Scandinavian Journal of Immunology via MedWorm.com

Modified Vaccination Technique for Prophylactic and Therapeutic Applications to Combat Endogenous Antigen–Induced Disorders

Scandinavian Journal of Immunology — Tue, 23 Feb 2010 13:37:28 +0100

Public health can be protected most effectively through vaccination programmes. However, while presently available vaccination techniques protects the individual by provoking immune responses against exogenous antigens (ags), such as those associated with certain bacteria and viruses, they cannot protect against or treat mishaps caused by endogenous ag. Recently, Barabas and colleagues have developed a new vaccination method, called modified vaccination technique (MVT), which allows the presentation of disease causing agents in such a way as to initiate and maintain desired immune response outcomes even in the context of mishaps associated with endogenous ag. For example, in an experimental autoimmune kidney disease, the MVT downregulated/terminated pathogenic immune responses that were ca...

Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis – a Paradoxical Effect of the Vector?

Scandinavian Journal of Immunology — Fri, 15 Jan 2010 13:37:41 +0100

A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-[gamma] and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU...

Autoantibodies to Neurotrophic Receptors TrkA, TrkB and TrkC in Patients with Acute Chagas' Disease

Scandinavian Journal of Immunology — Thu, 17 Dec 2009 00:00:00 +0100

Neurotrophic receptors TrkA and TrkC double up as receptors that Trypanosoma cruzi uses to invade cells and as autoantigen in T. cruzi-infected individuals (with Chagas' disease). Consequently, autoantibodies against TrkA and TrkC (ATA) potently block T. cruzi invasion in vitro and in ATA-immunized mice. Thus, ATA could keep T. cruzi invasion in check in Chagas' disease. However, ATA has been examined only in patients with chronic Chagas' disease. To determine whether ATA potentially participate in the early stage of infection, we analysed the sera of 15 patients with acute Chagas' disease, 4[ndash]66 years of age. We find that all sera contain high antibody titres to TrkA, TrkB and TrkC, but not to other growth factor receptors, indicating that ATA are produced relatively soon after T. cr...

LLT1-mediated Activation of IFN-γ Production in Human Natural Killer Cells Involves ERK Signalling Pathway

Scandinavian Journal of Immunology — Thu, 17 Dec 2009 00:00:00 +0100

Natural killer (NK) cell functions are regulated by a delicate balance of signals received through activating and inhibitory receptors expressed on the cell surface. Lectin-like transcript-1 (LLT1), expressed on a subpopulation of NK cells and other immune cells is a ligand for the NK cell inhibitory receptor, NKR-P1A (CD161). Previous studies showed that cross-linking surface LLT1 with a monoclonal antibody stimulated NK cell IFN-[gamma] secretion but had no effect on cytotoxicity. Here, we have examined the signalling pathways associated with LLT1-stimulated IFN-[gamma] secretion. We ligated LLT1 on NK92 cells with CD161 on target cells and analysed IFN-[gamma] production in the presence of pharmacological inhibitors specific for various signalling mechanisms. These results indicate that...

Innate IFN-γ Production by Subsets of Natural Killer Cells, Natural Killer T Cells and γδ T Cells in Response to Dying Bacterial-Infected Macrophages

Scandinavian Journal of Immunology — Thu, 17 Dec 2009 00:00:00 +0100

In this study, we showed that cell death of bone-marrow-derived macrophage (BMM) cells following in vitro infection with Staphylococcus aureus (SA), an extracellular bacterium, can also stimulate this IFN-[gamma] production pathway. We also unequivocally demonstrated by using BMM cells from IL-12-deficient mice that the bacterial-infected macrophage cell death-mediated IFN-[gamma] production can occur without IL-12 although the magnitude of the response is much smaller than that in the presence of IL-12. The enhancing effect of IL-12 on this response proved to be attributable to the negligible amounts (0.5[sim]1.5 pg/ml) of IL-12p70 but not to the large amounts of IL-12p40 that were both secreted by SA- and LM-infected macrophages. Taken all together, we propose that macrophage cell death ...

Cell-Mediated Immune Response and Th1/Th2 Cytokine Profile of B-T Constructs of F1 and V Antigen of Yersinia pestis

Scandinavian Journal of Immunology — Thu, 17 Dec 2009 00:00:00 +0100

Yersinia pestis, a Gram-negative bacterium, is the etiological agent of pneumonic and bubonic plague and still active in various regions of the world. Because plague is highly infectious and can readily spread by aerosolization, it poses a bioterrorism threat. The effective induction of mucosal as well as systemic immunity is an important attribute of an improved vaccine for plague. An alternative approach described here is the use of protective epitopes derived from immunodominant antigens (F1 and V) of Yersinia pestis. As T-cell immunity is also a major contributor of protection, microencapsulated B-T constructs of F1 and V antigen were used to immunize outbred and inbred mice through intranasal route, and lympho-proliferative response and cytokine profile of both Th1 and Th2 arms were m...

New Production of Eosinophils and the Corresponding Th1/Th2 Balance in the Lungs after Allergen Exposure in BALB/c and C57BL/6 Mice

Scandinavian Journal of Immunology — Thu, 17 Dec 2009 00:00:00 +0100

This study shows that there is a difference in the distribution of eosinophils in the lung between the C57BL/6 and BALB/c mice, but no difference in eosinophil production or Th1/Th2 balance. (Source: Scandinavian Journal of Immunology)

Antitumour Response of a Double Mutant of Staphylococcal Enterotoxin C2 with the Decreased Affinity for MHC Class II Molecule

Scandinavian Journal of Immunology — Tue, 15 Dec 2009 00:00:00 +0100

In this study, site-directed mutagenesis has been used to introduce alanine substitutions at Phe144 and Leu45 in the molecule. The mutant genes were cloned and expressed, and the corresponding proteins were purified by nickel agarose affinity chromatography. We found that the SEC2 mutant proteins could stimulate the proliferation of human peripheral blood lymphocytes and inhibit the growth of tumour cells as native SEC2. Furthermore, flow cytometry assay showed that mSEC2(F44A, L45A) drastically reduced the ability of the toxin to bind to MHC class II. Physiological parameters revealed that mSEC2(F44A, L45A) reduced significantly rat temperature compared with native SEC2 in vivo. Our results clearly suggest that this genetically modified SEC2 protein is less toxic and justifies its further...

Striking Activation of NALT and Nasal Passages Lymphocytes Induced by Intranasal Immunization with Cry1Ac protoxin

Scandinavian Journal of Immunology — Tue, 15 Dec 2009 00:00:00 +0100

Cry1Ac protoxin from Bacillus thuringiensis is a potent mucosal immunogen and adjuvant. When delivered intranasally (i.n.) Cry1Ac elicits significant antibody response and is able to improve vaccination against Naegleria fowleri infection, but the functional effects occurring in nasal lymphocytes when this protein is administered alone have not been determined. Here, we investigated the effects of i.n. immunization with Cry1Ac on antibody production, lymphocyte activation and cytokine production in lymphocytes from nasal-associated lymphoid tissue (NALT) and nasal passages (NP). Our results show that i.n. immunization with Cry1Ac induced significant specific IgA and IgG cell responses, especially in NP. Besides, it increased the proportion of lymphocytes expressing the activation markers C...

RNA Silencing in the Antiviral Innate Immune Defence – Role of DEAD-box RNA Helicases

Scandinavian Journal of Immunology — Tue, 15 Dec 2009 00:00:00 +0100

RNA silencing is an efficient biochemical tool for gene knock downs as well as physiological phenomenon playing a major role in diverse biological processes. Recent knowledge suggests that the same protein families which mediate the experimental RNA interference (RNAi) in the fruit fly Drosophila melanogaster cells also contribute to the antiviral host defence in both invertebrate model organisms and mammals. Additionally, another branch of RNA silencing, the microRNAs (miRNAs), has been recently described in the context of host defence. In several studies, miRNAs have been shown to regulate essential immune responses. This review summarizes basic concepts of RNAi and miRNAs, especially in the context of immune defence, focusing on the newly discovered role of DEAD-box helicases in the RNA...

IL-23 in the Pathogenesis of Rheumatoid Arthritis

Scandinavian Journal of Immunology — Tue, 15 Dec 2009 00:00:00 +0100

Interleukin-23 (IL-23) is a heterodimeric cytokine belonging to the IL-6/IL-12 family that plays a key role in several of autoimmune and inflammatory disorders. This family contains the 34 type I cytokine receptor chains and 27 ligands, which share structural and functional similarities, but on the other hand they display distinct roles in shaping Th cells responses. IL-12 family cytokines have not only proinflammatory effects but they also promote inflammatory responses. IL-23 is composed of the p40 subunit in common with IL-12, and with a unique p19 subunit. IL-23 binding to an IL-23 receptor expressed on dendritic cells, macrophages and monocytes triggers the activation of Jak2 and Tyk2, which in turn phosphorylates STAT1, STAT3, STAT4 and STAT5 as well as induce formation of STAT3-STAT...

Mucosally induced Immunological Tolerance, Regulatory T Cells and the Adjuvant Effect by Cholera Toxin B Subunit

Scandinavian Journal of Immunology — Fri, 11 Dec 2009 13:37:33 +0100

Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) ('oral tolerance') is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer the relevant Ag together with, and preferably linked to the non-toxic B subunit protein of cholera toxin (CTB). Oral, nasal or sublingual administration of such Ag/CTB conjugates or gene fusion proteins have been found to induce tolerance with superior efficiency compared with administration of Ag alone, including the suppression of various autoimmune disorders and allergies in animal models. In a proof-of-concept clinical trial in patients with ...

Antigen Analysis of Mycobacterium tuberculosis H37Rv Culture Filtrate Proteins

Scandinavian Journal of Immunology — Thu, 10 Dec 2009 00:00:00 +0100

(Source: Scandinavian Journal of Immunology)

About CD26high CD8+ Lymphocytes in Type 1 Diabetes Mellitus

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

(Source: Scandinavian Journal of Immunology)

Disturbances in some Gene Expression in T Regulatory Cells Separated from Children with Metabolic Syndrome

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

The metabolic syndrome (MS) is defined as a cluster of risk factors, including abdominal obesity, dyslipidaemia, glucose intolerance and hypertension, which increase the risk for coronary heart disease. The immunological aspects of obesity and MS, including the role of T regulatory cells, have been intensively investigated. The aim of this study was to determine whether there is any disturbance in T regulatory cells number and/or function in children with MS. The percentages of T regulatory cells in the peripheral blood of children fulfilling the International Diabetes Federation criteria of the disease (n = 47) were assessed. Treg cells were also separated for further analysis of multiple genes important in their function with the use of real-time RT-PCR. We did not observe any difference...

A Novel Heterophilic Antibody Interaction Involves IgG4

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

In conclusion, here is defined a novel heterophilic antibody interaction and is established the universality of the unique Fc[ndash]Fc binding, both involving IgG4. (Source: Scandinavian Journal of Immunology)

Role of TLR2 and TLR4 in Human Neutrophil Functions Against Paracoccidioides brasiliensis

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

In paracoccidioidomycosis, a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb), studies have focused on the role of neutrophils that are involved in primary response to the fungus. Neutrophil functions are regulated by pro- and anti-inflammatory cytokines. The molecular mechanisms involved in this process are not fully understood, but there are strong evidences about the involvement of toll-like receptors (TLR). We aimed at evaluating TLR2 and TLR4 expression on human neutrophils activated with GM-CSF, IL-15, TNF-[alpha] or IFN-[gamma] and challenged with a virulent strain of P. brasiliensis (Pb18). Moreover, we asked if these receptors have a role on fungicidal activity, H2O2 and IL-6, IL-8, TNF-[alpha] and IL-10 production by activated and challenged cells. All cyt...

Production of Cytokines During Interaction of Peripheral Blood Mononuclear Cells with Autologous Ovarian Cancer Cells or Benign Ovarian Tumour Cells

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

Cytokines produced by tumour and immune cells may play a significant role in a modulation of immune cells response against tumour. We investigated an ability of peripheral blood mononuclear cells (PBMC) of patients with early and advanced stages of ovarian cancer and from non-cancer patients to produce various cytokines in the presence or absence of autologous ovarian cancer (OC) cells or benign ovarian tumour (BOT) cells. Activated PBMC of patients with advanced stage of cancer produced slight amount of interferon [gamma] (IFN-[gamma]) and what's more, the production of IFN-[gamma] was decreased in the presence of OC cells. PBMC of patients with ovarian cancer or benign ovarian tumour generated comparable amounts of interleukin 6 and 10 (IL-6, IL-10), and transforming growth factor [beta]...

Alloreactivity but Failure to Reject Human Islet Transplants by Humanized Balb/c/Rag2−/−gc−/− Mice

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

A human islet transplant can cure patients with type 1 diabetes. A drawback of islet transplantation is the life-long immunosuppressive medication, often associated with severe side effects. Moreover, in spite of the immunosuppressive therapy, islets are lost in the majority of transplanted patients over time. An improved small animal model for studies on human islet allograft rejection mechanisms and the development of new measures for its prevention is clearly warranted. Here, we evaluated the potential of Balb/cRag2[minus]/[minus][gamma]c[minus]/[minus] mice carrying a human-like immune system (so-called humanized mice) as a tool for studies on the rejection of transplanted human islets. Human T cells from Balb/cRag2[minus]/[minus][gamma]c[minus]/[minus] mice, which as neonates had been...

Combination of CTL-associated Antigen-4 Blockade and Depletion of CD25+ Regulatory T Cells Enhance Tumour Immunity of Dendritic Cell-based Vaccine in a Mouse Model of Colon Cancer

Scandinavian Journal of Immunology — Mon, 30 Nov 2009 00:00:00 +0100

In this study, we tested the hypothesis that the combination of CTLA-4 blockade and depletion of Treg cells would improve the potency of dendritic cell (DC)-based vaccine in a clinically relevant mouse model, which is transgenic for both carcinoembryonic antigen (CEA) and HLA-A2 for the treatment of colon carcinoma in a therapeutic setting. We found that administration of anti-CD25 antibody prior to vaccination or systemic administration of anti-CTLA-4 antibody with the vaccine improved tumour-free survival against CEA-expressing tumours compared with mice immunized with DC-based vaccine alone. However, the efficacy of the vaccine proved to be most effective when anti-CTLA-4 antibody was combined with Treg inhibition. This vaccination strategy dramatically improved the tumour-free survival...

Professor emeritus Jacob B. Natvig, one of the founders of Scandinavian Journal of immunology, turns 75

Scandinavian Journal of Immunology — Thu, 12 Nov 2009 13:37:31 +0100

(Source: Scandinavian Journal of Immunology)

Identification of Rv2041c, a novel immunogenic antigen from Mycobacterium tuberculosis with serodiagnostic potential

Scandinavian Journal of Immunology — Wed, 11 Nov 2009 00:00:00 +0100

(Source: Scandinavian Journal of Immunology)

The CCR 5 D32 Polymorphism Differentiates Cardioembolism from Other Aetiologies of Ischaemic Cerebrovascular Diseases

Scandinavian Journal of Immunology — Wed, 11 Nov 2009 00:00:00 +0100

(Source: Scandinavian Journal of Immunology)

The Effect of Microenvironmental CD40 Signals on TRAIL- and Drug-induced Apoptosis in Follicular Lymphoma Cells

Scandinavian Journal of Immunology — Wed, 11 Nov 2009 00:00:00 +0100

Follicular lymphoma (FL) cells are malignant counterparts of germinal centre (GC) B cells. Microenvironment of FL B cells has an important role in the progression of FL and might also have an impact on the treatment of FL. CD40 is an important mediator of microenvironmental survival signals in GCs. Here we studied responses of CD40 signalling on TRAIL-, dexamethasone- and doxorubicin-induced apoptosis in three human FL cell lines. In two of the FL cell lines, CD40 protected cells from apoptosis which was entirely dependent on the activation of NF-[kappa]B. In one of the FL cell lines, CD40 induced apoptosis itself. However, inhibition of NF-[kappa]B induced apoptosis in all three FL cell lines. Therefore, our results indicate that inhibitors of NF-[kappa]B or critical downstream anti-apopt...

Case–Control Study of a HLA-G 14-bp Insertion-Deletion Polymorphism in Women with Recurrent Miscarriages

Scandinavian Journal of Immunology — Fri, 30 Oct 2009 00:00:00 +0100

In this study, a total of 526 Chinese women were genotyped for the +14-bp/[minus]14-bp polymorphism, including 137 who had recurrent miscarriages (three miscarriages: 86, four or more miscarriages: 51), 138 women who had experienced two abortions and 251 women with normal fertility as controls. The +14-bp homozygote sequence was more prominent among those with recurrent miscarriages (three or more recurrent miscarriages) in contrast to fertile control women. Significant difference was observed in the distribution of +14-bp/+14-bp genotype between controls and the recurrent abortions group with four or more abortions. A 14-bp insertion/deletion polymorphism in exon 8 has a possible role in HLA-G expression in certain cases of recurrent miscarriage. However, additional studies are needed in ...

Relevance of CD38 Expression on CD8 T Cells to Evaluate Antiretroviral Therapy Response in HIV-1-infected Youths

Scandinavian Journal of Immunology — Fri, 30 Oct 2009 00:00:00 +0100

Surrogate markers for monitoring immuno-virological discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) and non-responders (42.9%) to stable antiretroviral therapy for a minimum of 6 months, on the basis of viral load and CD4 T cells, comprehensively evaluated by CD38 expression on CD8 T lymphocytes [measured as CD38 antibody bound per CD8 T cell (CD38 ABC) and %CD38+ of total CD8 T cells (%CD38/CD8)]...

Immunoregulatory Effects of Carvedilol on Rat Experimental Autoimmune Myocarditis

Scandinavian Journal of Immunology — Fri, 30 Oct 2009 00:00:00 +0100

The cardioprotective effects of carvedilol were studied in a rat model of experimental autoimmune myocarditis (EAM). After immunization, rats were orally administered 10 mg/kg/day carvedilol (group C, n = 15) or a vehicle control (Group V, n = 12) for 3 weeks. On day 21, echocardiography and haemodynamic parameters, myocarditis areas, and cytokine concentrations were measured. Serum carvedilol concentrations ranged from 10.5 ± 2.6 to 31.7 ± 9.3 ng/ml over a 24 h period on day 20. Carvedilol decreased the myocarditis areas (23.07 ± 1.6 versus 33.65 ± 2.71%, P < 0.0001). The left ventricular fractional shortening and the absolute value of +dP/dt or [ndash]dP/dt were significantly higher in Group C. Heart rate, systolic blood pressure, left ventricular end-diastolic pressure and central v...

Notch-Regulation upon Dll4-Stimulation of TGFb-Induced Apoptosis and Gene Expression in Human B-Cell Non-Hodgkin Lymphomas

Scandinavian Journal of Immunology — Fri, 30 Oct 2009 00:00:00 +0100

In conclusion, our data does not support a unifying role of Notch in regulating apoptosis in B-NHL, but warns that gamma-secretase inhibitors may actually counteract apoptosis in some cases. (Source: Scandinavian Journal of Immunology)

Autoimmunity: limited progress for the patient, despite decades of research

Scandinavian Journal of Immunology — Thu, 29 Oct 2009 13:37:28 +0100

(Source: Scandinavian Journal of Immunology)

Retraction

Scandinavian Journal of Immunology — Tue, 27 Oct 2009 00:00:00 +0100

(Source: Scandinavian Journal of Immunology)

Characterization of CD25-Positive T Cells During Syngeneic Pregnancy: Production of Stimulatory Class II MHC Molecules

Scandinavian Journal of Immunology — Sat, 10 Oct 2009 00:00:00 +0100

Various studies demonstrate that immunosuppression vis-à-vis paternal alloantigens may play a role for successful pregnancy. However, if this theory is true, the question that remains unanswered is how do syngeneic pregnancies manage to produce viable embryos. In allogeneic murine pregnancies immunosuppression is mediated by regulatory CD25+/Foxp3/CTLA-4 T cells. In order to evaluate whether these cells also play a role in syngeneic pregnancies, CD25+CD4+ and CD25+CD8+ were isolated from spleens of pregnant mice and examined as to the expression of specific suppressive and stimulatory markers, cytokine and soluble MHC class II antigen production. Interestingly, the CD25+ cells and their products displayed an MHC-restricted stimulatory activity on total spleen cell proliferation assays. Al...

Application of an ELISA-elution Assay to Dissociate Digoxin-antibody Complexes in Immunoaffinity Chromatography

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

In this study, we used a modified enzyme-linked immunosorbent assay (ELISA)-elution technique as a screening tool to select specific elution conditions. We examined 12 different elution conditions for the removal of antibodies from a complex on an ELISA plate; 0.2 mol/l glycine-HCl (pH 2.5), 1.0 mol/l acetic acid (pH 2.5), 25% methanol (pH 2.5) and 3 mol/l NaSCN showed a higher elution efficiency. We conducted affinity chromatography with these four conditions for the purification of anti-digoxin antibodies from hyperimmune sera with a digoxin-specific column using [omega]-aminoalkyl derivatives of Sepharose 4B, whose elution efficiency was similar to that of ELISA. We also monitored the relative specific activities during elution from the digoxin-specific column. The optimum, general-purp...

T-Cell Responses and In Vivo Cytotoxicity in the Target Organ and the Regional Lymphoid Tissue During Airborne Infection with the Virulent Mycobacterium tuberculosis MT103 and its Lipid Mutant fadD26

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

To ascertain the in vivo role of mycobacterial lipids phthiocerol dimycocerosates (PDIM) in experimental murine tuberculosis (Tb), airways infection was used to compare the parental virulent clinical isolate MT103 with its mutant fadD26, lacking PDIM. Lungs were assessed as the Tb-target organ and mediastinal lymph nodes as the corresponding lymphoid tissue, in order to quantify: the major T-cell subsets (CD4+/CD8+/[gamma][delta]+) and their activation kinetics, bacillary burden, and in vivo cytotoxicity against inoculated target cells loaded with mycobacterial Ags. After 4 weeks, infection augmented total and activated CD4+ and CD8+ T cells in lungs and nodes mainly with MT103, while [gamma][delta]+ T cells increased earlier in nodes. MT103 bacillary burden was bigger and appeared earlier...

The Allogeneic but not Syngeneic Dendritic Cells Effectively Generated Regulatory T Cells from Total Cd4+ Population without Exogenous Cytokines

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

Dendritic cells (DC) play a critical role in both the expansion of natural regulatory T cells (nTreg) and conversion of induced Treg (iTreg) from their precursors. In the present study, we evaluated the potential of DC to generate Treg from total CD4+ population which contains both nTreg and the precursors, and found that allogeneic (allo-DC) but not syngeneic DC (syn-DC) could effectively generated Foxp3+ Treg from total CD4+ population in the absence of exogenous cytokines. Compared with freshly purified CD4+ T cells, allo-DC-stimulated CD4+ T cells showed increased percentage of CD4+CD25+Foxp3+ Treg by 5[ndash]7-folds while syn-DC-stimulated CD4+ T cells did not. Furthermore, we demonstrated that the significant amounts of endogenous IL-2 and TGF-[beta], at least partially, contributed ...

Immunization with Cry1Ac from Bacillus Thuringiensis Increases Intestinal IgG Response and Induces the Expression of FcRn in the Intestinal Epithelium of Adult Mice

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

We have shown that Cry1Ac protoxin from Bacillus thuringiensis is a potent mucosal and systemic immunogen with adjuvant properties. Interestingly, we have observed that Cry1Ac preferentially induces high specific IgG responses in intestinal fluid when it is intraperitoneally administered to mice; therefore, in the present study, we used this protocol, as a model to address the influence of systemic immunization on the induction of the intestinal IgG response. The data shown indicate that upon intraperitoneal immunization with Cry1Ac, significant intestinal specific IgG cell responses were produced in the lamina propria, accompanied by an increased frequency of intestinal IgG+ lymphocytes and epithelial cells containing IgG. Considering that FcRn is the receptor responsible for the transpor...

Structural Difference in the Complement Activation Site of Human IgG1 and IgG3

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

This report indicates the presence of structural differences between human IgG1 and IgG3 in the C1q binding site, and points to a specialization of the two isotypes with respect to complement activation. (Source: Scandinavian Journal of Immunology)

Human γδ T Cells Produce the Protease Inhibitor and Antimicrobial Peptide Elafin

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

In this study, we have investigated whether [gamma][delta] T cells can produce additional antimicrobial peptides. To this end, we have screened human [gamma][delta] T cell clones by RT-PCR for mRNA expression of a broad range of antimicrobial peptides. While [alpha]-defensins were absent and [beta]-defensins (HBD1) present only in rare [gamma][delta] T cell clones, elafin mRNA was induced by supernatant of Pseudomonas aeruginosa grown under static conditions. Elafin is a protease inhibitor that also displays antimicrobial activity. Constitutive intracellular expression of elafin was demonstrated by flow cytometry and Western blot analysis. Furthermore, trappin-2 (pre-elafin) could be immunoprecipitated in cell lysates but also in the supernatant of [gamma][delta] T cells stimulated by Ps. ...

Alkali-Degradation of Amyloid: An Ancient Method Useful for Making Monoclonal Antibodies Against Amyloid Fibril Proteins

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

The systemic amyloidoses constitute a group of life-threatening disorders at which one out of about 15 different proteins have polymerized into fibrils. Prognosis and treatment varies widely and depends on the biochemical type. Determination of this has usually to be performed by immunohistochemistry which is a challenge because of lack of monospecific antibodies that can be used on formaldehyde-fixed tissue sections. We have here used an old method to create immunogenic fragments of AL-amyloid fibrils by partial degradation and solubilization with sodium hydroxide. The mouse monoclonal antibody pwlam raised against this material, labelled AL-amyloid deposits of lambda origin strongly and specifically in sections of formaldehyde-fixed and paraffin-embedded tissues. (Source: Scandinavian Jo...

Neonatal Alloimmune Thrombocytopenia is Not What It was A Lesson Learned from a Large Prospective Screening and Intervention Program

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

Controversies regarding the pathophysiology of neonatal alloimmune thrombocytopenia (NAIT) has hampered the development of consensus about how to identify, follow up and treat the women and children with this serious complication. One reason for this is that knowledge about the condition derived from previous retrospective studies do not necessarily conform with data derived from prospective investigations. The main obstacle to introduction of general screening programs to identify the pregnancies to treat, have been lack of reliable risk factors, and an effective treatment. Now, several recent prospective screening programs including up to 100,000 pregnant women has changed the understanding of the NAIT-pathology, and has shown that we are close to answering these critical questions. (Sou...

Review: To What Extent are T Cells Tolerant to Immunoglobulin Variable Regions?

Scandinavian Journal of Immunology — Wed, 30 Sep 2009 00:00:00 +0100

During the last 25 years it has become increasingly clear that short peptides derived from Ig V-regions are displayed on MHC class II molecules. Recognition of such idiotypic(Id)-peptide/MHC class II complexes by Id-specific CD4+ T cells plays a role in (1) Id-driven T-B collaboration, (2) immunosurveillance of B cell cancers and (3) Id-vaccination. A crucial question is then: to what extent are T cells tolerized to Ig V-region sequences? Or rephrased: how large is the T-cell repertoire for Ig V-region sequences presented by MHC class II molecules? We argue that T cells are to a large extent tolerant to germline-encoded V-region sequences but that there is a T-cell repertoire for rare Id-sequences that arise as a consequence of somatic hyper mutation or N-region diversity. Moreover, when o...

Complement Receptor 1 (A3650G RsaI and Intron 27 HindIII) Polymorphisms and Risk of Gallbladder Cancer in North Indian Population

Scandinavian Journal of Immunology — Thu, 24 Sep 2009 00:00:00 +0100

Decreased expression due to genetic variations in complement receptor 1 (CR1) on erythrocytes might result in reduced clearance of immune complexes, conferring interindividual variation for gallbladder cancer (GBC) susceptibility. We studied role of CR1 (A3650G RsaI and Intron 27 HindIII) polymorphisms in gallstone disease and GBC in north Indian population. Study included 185 GBC patients, 185 gallstone patients and 200 controls. Genotyping was done by PCR-RFLP. Result showed GG genotype and G allele of CR1 A3650G RsaI were conferring significant risk for GBC [(P = 0.022; OR = 1.94; 95% CI = 1.1[ndash]3.4) and (P = 0.035; OR = 1.35; 95% CI = 1.0[ndash]3.8) respectively]. Also, comparison of GBC patients with gallstone patients showed increased risk for GBC in presence of GG genotype and G...

HIV-infected Patients with a Large Thymus Maintain Higher CD4 Counts in a 5-year Follow-up Study of Patients Treated with Highly Active Antiretroviral Therapy

Scandinavian Journal of Immunology — Thu, 24 Sep 2009 00:00:00 +0100

In conclusion, the importance of the thymus to the rate of cellular restoration seems primarily to lie within the first two years of HAART. However, patients with larger thymic size are able to maintain higher CD4 counts even after 5 years of HAART. (Source: Scandinavian Journal of Immunology)

Feedback Regulation of Mitochondria by Caspase-9 in the B Cell Receptor-Mediated Apoptosis

Scandinavian Journal of Immunology — Thu, 24 Sep 2009 00:00:00 +0100

During the germinal centre reaction (GC), B cells with non-functional or self-reactive antigen receptors are negatively selected by apoptosis to generate B cell repertoire with appropriate antigen specificities. We studied the molecular mechanism of Fas/CD95- and B cell receptor (BCR)-induced apoptosis to shed light on the signalling events involved in the negative selection of GC B cells. As an experimental model, we used human follicular lymphoma (FL) cell line HF1A3, which originates from a GC B cell, and transfected HF1A3 cell lines overexpressing Bcl-xL, c-FLIPlong or dominant negative (DN) caspase-9. Fas-induced apoptosis was dependent on the caspase-8 activation, since the overexpression of c-FLIPlong, a natural inhibitor of caspase-8 activation, blocked apoptosis induced by Fas. In...

Levels of Dendritic Cell Populations and Regulatory T Cells Vary Significantly Between Two Commonly Used Mouse Strains

Scandinavian Journal of Immunology — Thu, 24 Sep 2009 00:00:00 +0100

Dendritic cells (DC) are a heterogeneous group of professional antigen-presenting cells (APC) involved in both initiating immune responses and maintaining tolerance. Roughly, DC can be divided into plasmacytoid DC (pDC) and conventional DC (cDC). By controlling regulatory T cells (Treg), DC can influence the outcome of both immunity and autoimmunity. Since the use of mice as in vivo models became a practical tool for researchers studying pathological events in all kind of human diseases, we decided to compare levels of cDC, pDC and Treg in both spleen and blood between two inbred mouse strains. Here we show that two commonly used mouse strains, BALB/c and C57BL/10J mice, have significantly different levels of distinct CD11c+/CD4[ndash]/CD8a+, CD11c+/CD4+/CD8a[ndash] and CD11c+/CD4[ndash]/C...

Does our Current Understanding of Immune Tolerance, Autoimmunity, and Immunosuppressive Mechanisms Facilitate the Design of Efficient Cancer Vaccines?

Scandinavian Journal of Immunology — Thu, 17 Sep 2009 00:00:00 +0100

The therapeutic use of the immune system to attack cancer cells has been a longstanding vision among tumour immunologists. However, most human tumours are poorly immunogenic and are able to invade the host immune system. Although these obstacles are clearly critical to cancer vaccine development, the induction of a strong anti-tumour immune response may rely on the activation of high affinity T cells through a molecular mimicry mechanism which involves cross-reactive recognition of foreign antigens mimicking the structure of tumour proteins. Taking into account the disparity in HLA molecules needed to present shared antigens; in late 1990s Stauss et al. described the possibility of generating allorestricted high affinity cytotoxic T cells against synthetic self-peptides bound to non-self-M...

Common CCR 5 Polymorphism in Stroke The CCR 5 Δ32 Polymorphism Differentiates Cardioembolism from Other Aetiologies of Ischaemic Cerebrovascular Diseases

Scandinavian Journal of Immunology — Thu, 17 Sep 2009 00:00:00 +0100

Inflammation is involved in the development of atherosclerosis. The CC chemokine receptor 5 (CCR5) initiates chemotaxis and modulates the inflammation secondary to atherosclerosis and related vascular diseases. The CCR5 [Delta]32 polymorphism influences the expression of CCR5 on the cell surface. The purpose of this study was to examine the effect of the [Delta]32 polymorphism in ischaemic cerebrovascular disease (ICVD). The CCR5 [Delta]32 polymorphism was genotyped in 1462 individuals: 562 ischaemic stroke (IS), 97 transient ischaemic attack (TIA) and in 803 healthy controls. All 659 ICVD patients were categorized according to the Trial of Org 10172 in Acute Stroke Treatment aetiological classification. The investigated subtypes were large artery atherosclerosis (LAA), cardioembolism (CE)...

New Alternative Vaccine Component Against Mycobacterium Tuberculosis– Heat Shock Protein 16.3 or its T-Cell Epitope

Scandinavian Journal of Immunology — Thu, 17 Sep 2009 00:00:00 +0100

Heat shock protein 16.3 (Hsp16.3) of Mycobacterium tuberculosis (MTB) containing T-cell and B-cell epitopes not only plays an important role in the survival of MTB against macrophages, but also has great potential to be used to develop new TB vaccines. In order to study whether Hsp16.3 can be replaced with its T-cell epitope for producing a vaccine against TB, we expressed and purified Hsp16.3 protein of MTB H37Rv strain and confirmed by immunoblotting. The immune responses and protection against the H37Rv induced by Hsp16.3 protein were compared with its T-cell epitope synthetic peptide in mice. The results showed that both Hsp16.3 and its synthetic peptide induced significantly stronger specific antibodies than the classical TB vaccine[ndash]BCG (bacillus Calmette-Guérin). Compared with...

Identification of Rv2041c, a Novel Immunogenic Antigen from Mycobacterium tuberculosis with Serodiagnostic Potential

Scandinavian Journal of Immunology — Thu, 17 Sep 2009 00:00:00 +0100

In this study, recombinant (r)Rv2041c was produced in Escherichia coli to examine its role in immune responses. Increased Rv2041c expression in vitro during dormancy and during infection in human macrophages was confirmed by Western blotting and reverse transcription polymerase chain reaction, respectively. Interestingly, positive antibody responses to rRv2041c were detected only in those patients with active tuberculosis (TB) and in mice infected with M. tuberculosis H37Rv. Finally, Rv2041c was used successfully in the serodiagnosis of active M. tuberculosis infection in Korean patients in conjunction with other M. tuberculosis proteins, including Ag85 complex, 38 kDa, rESAT-6, rHSP-X and rCFP-10. Our Rv2041c[ndash]ELISA had comparable diagnostic sensitivity and equivalent specificity to ...

Mucosal Immunity: Induction, Dissemination, and Effector Functions

Scandinavian Journal of Immunology — Thu, 10 Sep 2009 00:00:00 +0100

Prevention of infections by vaccination remains a compelling goal to improve public health. Most infections involve the mucosae, but the development of vaccines against many of these pathogens has yet to be successful. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion [ndash] a term coined for non-inflammatory antibody shielding of internal body surfaces [ndash] mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA) [ndash] produced by local plasma cells stimulated by antigens that target the mucosae. SIgA was early shown to be complexed with an epithelial glycoprotein [ndash] the secretory component (SC). In 1974, a common SC-...

Immune Responses in Patients with Metastatic Renal Cell Carcinoma Treated with Dendritic Cells Pulsed with Tumor Lysate

Scandinavian Journal of Immunology — Thu, 10 Sep 2009 00:00:00 +0100

In this study, we analysed lysate specific proliferation of PBMCs from these patients together with the TH1/TH2 balance of the responding T cells. Also, serum concentrations of IL-10, IL-12, IL-15, IL-17 and IL-18 from these patients and additional thirteen HLA-A2 positive mRCC patients treated with autologous DC pulsed with survivin and telomerase peptides were analysed during vaccination to identify systemic immune responses and potential response biomarkers. In HLA-A2 negative mRCC patients a spontaneous predominance of TH1 secreting tumour lysate specific T cells was observed prior to vaccination in patients attaining stable disease (SD) during treatment whereas patients with continued progressive disease (PD) had a mixed TH1/TH2 response. The TH1/TH2 balance was unchanged during vacci...

A Comparative Study of Transfection Methods for RNA Interference in Bone Marrow-Derived Murine Dendritic Cells

Scandinavian Journal of Immunology — Thu, 10 Sep 2009 00:00:00 +0100

In conclusion, this protocol was effective for manipulation of murine BM-DC function through the use of specific siRNA and such methods can be important for the future study of DC[ndash]T cell interactions. (Source: Scandinavian Journal of Immunology)

On the Sorting of the Repertoire: An analysis of Cohn's challenge to Integrity (Dembic), Round 2

Scandinavian Journal of Immunology — Mon, 31 Aug 2009 23:00:00 +0100

In analyzing the integrity model and other context-based models, Melvin Cohn excluded the possibility that regulatory T cells or germline selected mechanisms can contribute to defining the specificity of immune responses. Here I discuss in greater detail how both the experimental data and a quantitative view of the evolution of immune control mechanisms challenge Cohn's arguments. (Source: Scandinavian Journal of Immunology)

Insulin2 Gene (Ins2) Transcription by NOD Bone Marrow-derived Cells Does Not Influence Autoimmune Diabetes Development in NOD-Ins2 Knockout Mice

Scandinavian Journal of Immunology — Wed, 26 Aug 2009 00:00:00 +0100

Insulin is a critical autoantigen for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. About 80% of NOD females and 30[ndash]40% of NOD males develop diabetes. However, Insulin2 (Ins2) knockout NOD mice develop autoimmune diabetes with complete penetrance in both sexes, at an earlier age, and have stronger autoimmune responses to insulin. The severe diabetes phenotype observed in NOD-Ins2[minus]/[minus] mice suggests that lack of Ins2 expression in the thymus may compromise immunological tolerance to insulin. Insulin is a prototypical tissue specific antigen (TSA) for which tolerance is dependent on expression in thymus and peripheral lymphoid tissues. TSA are naturally expressed by medullary thymic epithelial cells (mTEC), stromal cells in peripheral lymphoid tissu...

TLR9 Activation Increases TAP-Independent Vesicular MHC Class I Processing In vivo

Scandinavian Journal of Immunology — Wed, 26 Aug 2009 00:00:00 +0100

Cross-presentation of soluble protein antigens on major histocompatibility complex (MHC) class I by dendritic cells (DC) can occur in vesicular, endolysosomal compartments and be either dependent or independent of TAP peptide transporters. Here we investigate if an immunostimulatory CpG oligodeoxynucleotide can increase the activity in a TAP-independent endolysosomal vesicular pathway (el-VP) in vivo as we have earlier found in in vitro cultured DC. We use the in vivo response of CFSE labelled OT-1 T cells, transgenic for a T-cell receptor (TCR) that recognizes an ovalbumin (OVA)-derived peptide (SIINFEKL) presented by H-2Kb, transferred into TAP1[minus]/[minus] mice, as a functional read-out for activity in the el-VP. We have found a poor OT-1 T-cell response to soluble OVA which, however...

Effects of Lipopolysaccharide on the Induction of Mixed Chimerism in Cyclophosphamide-Induced Tolerance

Scandinavian Journal of Immunology — Wed, 26 Aug 2009 00:00:00 +0100

In conclusion, LPS-infusion had little influence on the immune response of donor-reactive T cells, but had a significant effect on the induction and maintenance of mixed chimerism in CP-induced tolerance. (Source: Scandinavian Journal of Immunology)

Use of Immobilized HLA-A2:Ig Dimeric Proteins to Determine the Level of Epitope-Specific, HLA-Restricted CD8+ T-Cell Response

Scandinavian Journal of Immunology — Wed, 26 Aug 2009 00:00:00 +0100

A novel assay to assess antigen-specific cytokine release from stimulated CD8+ T cells derived from the mucosal and peripheral blood compartments has been developed and standardized using the influenza A virus matrix protein (MP) peptide, GILGFVFTL. This technology is based on the capacity for the human leucocyte antigen (HLA)-A2:Ig dimeric protein to stimulate CD8+ T cells in a major histocompatibility complex (MHC) class I-restricted fashion without the necessity for antigen presenting cells (APC). This assay has been optimized utilizing a 9-amino acid residue (9mer) peptide, the optimal peptide length for presenting an epitope to CD8+ T cells. Compared to existing assays, this more sensitive and specific methodology requires fewer cells, enabling easier and more accurate monitoring of t...

Serum Soluble Interleukin-2 Receptor, Beta2-Microglobulin, Lactate Dehydrogenase and Erythrocyte Sedimentation Rate in Children with Hodgkin's Lymphoma

Scandinavian Journal of Immunology — Fri, 21 Aug 2009 00:00:00 +0100

The study was to determine clinical utility of serum soluble interleukin (IL)-2 receptor (sIL-2R[alpha]), [beta]2-microglobulin ([beta]2-M), lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR) as markers of diagnosis, prognosis and monitoring of response to therapy in childhood Hodgkin's lymphoma (HL). The markers were measured prospectively before treatment and in complete remission (CR) during and after therapy in 30 children with HL (F/M:19/11; median age: 11.3 years) and once in 50 healthy children (F/M: 24/26; median age: 8.7 years). Median pretreatment levels of all analysed markers were significantly higher than in healthy controls. Increased pretreatment sIL-2R[alpha], LDH and ESR correlated with bulky disease; sIL-2R[alpha], [beta]2-M and ESR with presence of B sy...

Lipoxin A4 Metabolites/Analogues from Two Commercial Sources have No Effects on TNF-α-mediated Priming or Activation through the Neutrophil Formyl Peptide Receptors

Scandinavian Journal of Immunology — Tue, 18 Aug 2009 23:00:00 +0100

In this study, we examined the influence of metabolically stable LXA4 analogues on the biological activities induced by a previously characterized FPR2 agonist (WKYMWM) and a commonly used FPR1 agonist (fMLF). We also investigated the analogues regarding their direct effect on TNF[alpha]-mediated neutrophil mobilization of the complement receptor 3 (CR3) and their indirect effect on cytokine-dependent priming of the cells. The LXA4 analogues we used came from two commercial sources. In our experiments, they did not induce any direct neutrophil response, nor did they affect the increase in the number of CR3 molecules on the neutrophil surface or the primed response. Therefore, we conclude that these LXA4 analogues do not have an impact on TNF-[alpha] induced signalling in neutrophils. We al...

Effects of Salivary Gland Homogenate from Wild-Caught and Laboratory-Reared Lutzomyia longipalpis on the Evolution and Immunomodulation of Leishmania (Leishmania) amazonensis Infection

Scandinavian Journal of Immunology — Tue, 18 Aug 2009 23:00:00 +0100

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated subcutaneously into the hind footpads or into the ear dermis with 106 promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our fi...

Regions of Differences Encoded Antigens as Targets for Immunodiagnosis of Tuberculosis in Humans

Scandinavian Journal of Immunology — Tue, 18 Aug 2009 23:00:00 +0100

This article provides an overview of the use of RD antigens in the immunodiagnosis of tuberculosis infection and disease. (Source: Scandinavian Journal of Immunology)

Editorial

Scandinavian Journal of Immunology — Tue, 18 Aug 2009 10:01:44 +0100

(Source: Scandinavian Journal of Immunology)

Hans G Boman (1924-2008): Pioneer in Peptide-Mediated Innate Immune Defence

Scandinavian Journal of Immunology — Mon, 17 Aug 2009 23:00:00 +0100

(Source: Scandinavian Journal of Immunology)

Anomalous Immunogenic Properties of Serine Proteases

Scandinavian Journal of Immunology — Thu, 16 Jul 2009 23:00:00 +0100

It has previously been shown that a [sim]27 kDa serine protease of Schistosoma mansoni larvae, the cercarial elastase (CE), was a poor immunogen in as much as it failed to induce an antibody response. The CE has a critical role in enabling schistosome larvae to penetrate the skin of their definitive hosts, so the apparently poor immunogenicity of this enzyme is clearly of interest. To understand its lack of immunogenicity better and in particular to determine whether it is related to its proteolytic activity, we have measured antibody responses of mice to three different serine proteases. Groups of mice were immunized with porcine pancreatic trypsin (TRY), chymotrypsin (CHY) or elastase (ELA) and the resulting antibody response compared with antibody responses to two non-protease antigens,...

The CD4+CD8+ and CD4+ Subsets of FOXP3+ Thymocytes Differ in their Response to Growth Factor Deprivation or Stimulation

Scandinavian Journal of Immunology — Thu, 16 Jul 2009 23:00:00 +0100

The timing of thymic regulatory T (Treg) cell commitment remains unclear. Specifically, there is disagreement as to whether the CD4+CD8+ FOXP3+ thymocytes are precursors of mature CD4+ FOXP3+ Treg cells, or an independent Treg cell lineage. We reasoned that precursors should be more susceptible to apoptosis than mature Treg cells, and tested this by growth factor removal and anti-CD3 stimulation. Both treatments resulted in an increase of CD4+ FOXP3+ thymocytes, whereas the frequency of CD4+CD8+ FOXP3+ thymocytes decreased significantly. These changes were accompanied by an increase of annexin+ apoptotic cells. Both of these FOXP3+ subsets expressed higher levels of Bcl-2 and BIM than other thymocytes, and while in our setting expression of BIM seemed to predispose the cells to apoptosis, ...

In vivo Extravasated Human Monocytes have an Altered Expression of CD16, HLA-DR, CD86, CD36 and CX3CR1

Scandinavian Journal of Immunology — Thu, 16 Jul 2009 23:00:00 +0100

The phenotypic alterations in monocytes induced by extravasation in vivo are still largely unknown. We addressed the question whether a general phenotype of extravasated monocytes exists and whether this phenotype differs between healthy individuals and statin treated patients with coronary artery disease (CAD). In vivo extravasated monocytes from CAD patients and healthy controls were collected by use of the skin blister method and compared with peripheral circulating monocytes by flow cytometry. The number of CD14+CD16+ monocytes were significantly higher in the skin blister compared with peripheral circulation in both patients (P < 0.001) and controls (P = 0.005). In vivo extravasated monocytes had in comparison with peripheral monocytes a lower expression of CX3CR1, a higher expression...

How do Regulatory T Cells Work?

Scandinavian Journal of Immunology — Thu, 16 Jul 2009 23:00:00 +0100

CD4+ T cells are commonly divided into regulatory T (Treg) cells and conventional T helper (Th) cells. Th cells control adaptive immunity against pathogens and cancer by activating other effector immune cells. Treg cells are defined as CD4+ T cells in charge of suppressing potentially deleterious activities of Th cells. This review briefly summarizes the current knowledge in the Treg field and defines some key questions that remain to be answered. Suggested functions for Treg cells include: prevention of autoimmune diseases by maintaining self-tolerance; suppression of allergy, asthma and pathogen-induced immunopathology; feto-maternal tolerance; and oral tolerance. Identification of Treg cells remains problematic, because accumulating evidence suggests that all the presently-used Treg mar...

Differential Gene Expression in CD45+ Cells at Para-aortic Foci Stage of Chicken Haematopoiesis

Scandinavian Journal of Immunology — Sun, 05 Jul 2009 23:00:00 +0100

Para-aortic foci of chicken embryos at 6[ndash]7 days of development are considered to provide a microenvironment for haematopoietic stem cell proliferation and initial differentiation similar to that of fetal liver in mammals. Here, we have investigated the genes involved in this process by constructing and analysing a subtractive cDNA library from CD45+ cells in para-aortic region. Among 394 analysed clones 99 distinct genes were identified by sequence homology search. Classification of the identified genes according to biological processes revealed that innate immunity-related genes are highly expressed at this stage. This can be explained by the presence of yolk sac-derived macrophages in the original tissue sample but also by the indiscriminate expression of multiple lineage-specific ...

Impaired Antibody Responses but Normal Proliferation of Specific CD4+ T Cells in Mice Lacking Complement Receptors 1 and 2

Scandinavian Journal of Immunology — Tue, 30 Jun 2009 23:00:00 +0100

Severely impaired Ab responses are seen in animals lacking C (complement) factors C2, C3 or C4 as well as CR1/2 (C receptors 1 and 2). The molecular mechanism behind this phenomenon is not understood. One possibility is that C-containing immune complexes are endocytosed via CR2 on B cells and presented to specific CD4+ T cells, which would then proliferate and provide efficient help to specific B cells. In vitro, B cells can endocytose immune complexes via CR1/2 and present the Ag to T cells. Whether absence of this Ag presenting function in Cr2[minus]/[minus] mice (mice lacking CR1/2) explains their low Ab response is unclear. To address this question, Cr2[minus]/[minus] and wild type mice were transferred with OVA-specific T cells, obtained from the DO11.10 strain which has a transgenic ...

Post-consolidation Immunotherapy with Histamine Dihydrochloride and Interleukin-2 in AML

Scandinavian Journal of Immunology — Tue, 23 Jun 2009 23:00:00 +0100

The initial chemotherapy in acute myeloid leukaemia (AML) comprises a first phase of induction and a second phase of consolidation. In the majority of patients, the induction treatment leads to complete remission (CR), defined as microscopic disappearance of leukaemic disease along with the return of normal haematopoiesis. However, despite the introduction of more efficacious consolidation regimens, a worryingly large proportion of AML patients in CR will subsequently experience relapses with poor prospects of long-term survival. A relapse is assumed to be the result of expansion of residual leukaemic cells that have escaped the initial chemotherapy. The anti-leukaemic functions of T cells and natural killer (NK) cells has formed the background to the use of interleukin-2 (IL-2), a T- and ...

Reduced Apoptosis of Mouse Macrophages Induced by yscW Mutant of Yersinia pestis Results from the Reduced Secretion of YopJ and Relates to Caspase-3 Signal Pathway

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system (T3SS) that injects six Yersinia outer protein (Yop) effector proteins into the cytosol of macrophages, leading to disruption of host defence mechanisms. Here, we report that a T3SS structural protein YscW of Yersinia pestis contributed to the induction of apoptosis of murine macrophages. The apoptotic percentage of macrophages, from both mouse peritoneal cavity and spleen, and of RAW264.7 cell line, caused by the yscW mutant strain was significantly lower than that by wild type (WT) Y. pestis and yscW complemented strain. Meanwhile, detection of caspase-3 activity in macrophages, a key apoptosis-inducing protein, showed coincident results with the changes of macrophage apoptosis induced...

A Systematic Review and Meta-analysis of the Efficacy and Safety of Etanercept for Treating Rheumatoid Arthritis

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

The aim of this study was to evaluate the efficacy and safety of etanercept (ETA) for treating rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials comparing subcutaneous doses of ETA at 25 mg twice a week or 50 mg weekly to a placebo group, with or without methotrexate. Studies of low quality (less than 3 points on Jadad's scale) were excluded. The efficacy was assessed by using the criteria of the American College of Rheumatology (ACR). Safety data were evaluated based on serious adverse events, serious infections, malignancy and deaths. Withdrawals as a result of adverse events or lack of efficacy were also evaluated. Eight studies met the inclusion criteria, comprising 2385 patients. In the efficacy meta-analysis, a greater number of ETA-trea...

Increased Expression of Activation-Induced Cytidine Deaminase is Associated with Anti-CCP and Rheumatoid Factor in Rheumatoid Arthritis

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

Rheumatoid arthritis (RA) is associated with higher levels of autoantibodies and IL-17. Here, we investigated if ectopic lymphoid follicles and peripheral blood mononuclear cells (PBMCs) from RA patients exhibit increased activation-induced cytidine deaminase (AID), and if increased AID is correlated with serum levels of autoantibodies and IL-17. The results of immunohistochemical staining showed that organized AID+ germinal centres were observed in six of the 12 RA synovial samples, and AID+ cells were found almost exclusively in the B-cell areas of these follicles. Aggregated but not organized lymphoid follicles were found in only one OA synovial sample without AID+ cells. Significantly higher levels of AID mRNA (Aicda) detected by RT-PCR were found in the PBMCs from RA patients than PBM...

Studies on the Mechanism by Which Antigen-Specific IgG Suppresses Primary Antibody Responses: Evidence for Epitope Masking and Decreased Localization of Antigen in the Spleen

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

Immunoglobulin (IgG) has the ability to suppress the Ab response against the Ag to which it binds. Although the mechanism remains unclear, this phenomenon has physiological relevance and is used clinically in Rh prophylaxis. As suppression works well in mice lacking the inhibitory Fc[gamma]RIIB, the two most likely explanations are that IgG masks epitopes and/or that IgG increases the clearance of Ag. In the present study, mice were immunized with sheep red blood cells (SRBC) to which the hapten 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP) was conjugated at high or low density and the ability of IgG anti-NIP to suppress the Ab response to NIP and SRBC was assayed. Only the NIP-specific response was suppressed when mice were immunized with SRBC-NIPlow, whereas both NIP- and SRBC-specific respo...

HIV Induces both a Down-Regulation of IRAK-4 that Impairs TLR Signalling and an Up-regulation of the Antibiotic Peptide Dermcidin in Monocytic Cells

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

In this study, the effects of HIV infection on the protein profile of undifferentiated monocyte-like THP-1 cells were examined by a mass spectrometric approach based on stable isotope labelling with amino acid in cell culture (SILAC). We identified 651 proteins, of which nine proteins were down-regulated and 17 proteins were up-regulated in HIV-infected THP-1 cells as compared to uninfected controls. Most remarkably, the IL-1 receptor associated kinase 4 (IRAK-4), which is essential for virtually all TLR signalling, was suppressed, whereas the precursor for the antibiotic peptide Dermcidin was up-regulated in HIV-infected cells. Upon stimulation of either TLR2 or TLR4, the HIV-infected THP-1 cells displayed reduced TNF-[alpha] secretion. The HIV-induced down-regulation of IRAK-4 was reconf...

Mycobacterium tuberculosis Entry into Mast Cells Through Cholesterol-rich Membrane Microdomains

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

Cholesterol-enriched membrane microdomains (lipid rafts) play a role in the uptake of many pathogens. Mycobacteria are one of the intracellular pathogens that utilize lipid rafts in order to invade both phagocytic and non-phagocytic cells. However, the mechanism of Mycobacterium tuberculosis uptake by mast cell is not known. To address this issue, we investigated the interaction of M. tuberculosis (H37Rv strain) with mast cells. Confocal microscopy showed that interaction of mycobacterium with mast cell resulted in changes in the mast cell surface, with formation of pseudopod-like structure and activation with visibly extruded granules. Moreover, infection of mast cells with Mycobacteria induced cholesterol accumulation at the site of bacterial entry and around intracellular mycobacteria. ...

MHC II and the Endocytic Pathway: Regulation by Invariant Chain

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

The major histocompatibility complex (MHC) class I and II molecules perform vital functions in innate and adaptive immune responses towards invading pathogens. MHC class I molecules load peptides in the endoplasmatic reticulum (ER) and display them to the T cell receptors (TcR) on CD8+ T lymphocytes. MHC class II molecules (MHC II) acquire their peptides in endosomes and present these to the TcR on CD4+ T lymphocytes. They are vital for the generation of humoral immune responses. MHC II assembly in the ER and trafficking to endosomes is guided by a specialized MHC II chaperone termed the invariant chain (Ii). Ii self-associates into a trimer in the ER, this provides a scaffold for the assembly of three MHC II heterodimers and blocks their peptide binding grooves, thereby avoiding premature...

The Role of Extracellular DNA in Autoimmunity in SLE

Scandinavian Journal of Immunology — Mon, 22 Jun 2009 23:00:00 +0100

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the expression of antibodies to DNA. These antibodies form immune complexes that can stimulate cytokine production as well as deposit in the tissues to incite inflammation and damage. For the formation of immune complexes, the availability of extracellular DNA in an immunologically relevant form is essential. While apoptosis has been implicated as the source of this nuclear material in SLE, as shown with in vitro or in vivo systems, extracellular DNA can originate from apoptotic as well as necrotic cells. In experimental models, the release of DNA occurs with the administration of cells induced to die, in vitro as well as the administration of agents to induce cell death in situ. This release can be infl...

Peripheral Immune Response in Pulmonary Tuberculosis

Scandinavian Journal of Immunology — Sun, 21 Jun 2009 23:00:00 +0100

In conclusion we suggest that, CD8+ T cells producing both Th1 and Th2 type cytokines, may play important role in the peripheral immune response to mycobacteria. (Source: Scandinavian Journal of Immunology)

Folate-Metabolizing Genes in Lymphoma Patients from Sweden

Scandinavian Journal of Immunology — Sun, 14 Jun 2009 23:00:00 +0100

(Source: Scandinavian Journal of Immunology)

The Elevated Interferon Gamma Production is an Important Immunological Marker in HAM/TSP Pathogenesis

Scandinavian Journal of Immunology — Sun, 14 Jun 2009 23:00:00 +0100

Human T-lymphotropic virus type 1 (HTLV-1) is the agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may occur in >5% of patients during their lifetime. HTLV-1-infection causes disturbances in the immune system, and the viral load may also play an important role in the pathogenesis of HAM/TSP. Some cytokines are involved in the pathogenesis of this disorder. We have determined IL-2, IL-4, IL-10, IL-12 p70, IFN-[gamma] and TNF-[alpha] production among HTLV-1-infected subjects from our HTLV-out Clinic in Institute of Infectious 'Emílio Ribas' in Sao Paulo city, Brazil. PBMC obtained from healthy controls (n = 32), asymptomatic HTLV-1 carriers (n = 68) and HAM/TSP patients (n = 44) were grown in the absence and in the presence of phytohaemagglutinin (PHA)...

Toll-Like Receptor Expression and Function in Subsets of Human γδ T Lymphocytes

Scandinavian Journal of Immunology — Sun, 14 Jun 2009 23:00:00 +0100

Two subsets of human [gamma][delta] T cells can be identified by T cell receptor (TCR) V gene usage. V[delta]2V[gamma]9 T cells dominate in peripheral blood and recognize microbe- or tumour-derived phosphoantigens. V[delta]1 T cells are abundant in mucosal tissue and recognize stress-induced MHC-related molecules. Toll-like receptors (TLRs) are known to co-stimulate interferon-[gamma] (IFN-[gamma]) production in peripheral blood [gamma][delta] T cells and in V[delta]2V[gamma]9 T cell lines. By microarray analysis, we have identified a range of genes differentially regulated in freshly isolated [gamma][delta] T cells by TCR versus TCR plus TLR3 stimulation. Furthermore, we have investigated TLR expression in freshly isolated V[delta]1 and V[delta]2 subsets and cytokine/chemokine production ...

The Role of Natural Killer Cells in Resistance to the Intracellular Bacterium Listeria monocytogenes in Rats

Scandinavian Journal of Immunology — Sun, 14 Jun 2009 23:00:00 +0100

We have investigated the influence of early innate immune resistance mechanisms on infection with the intracellular bacterium Listeria monocytogenes in rats. Rats were injected i.v. with various amounts of Listeria and the number of bacterial colonies in the spleen was determined at different time points after infection. A bacterial dose as low as 2 × 104 cells gave reproducible infection within the spleen. Athymic nude rats lacking normal T cells but with a robust NK cell repertoire for MHC antigens were more resistant to bacterial replication within the spleen than were normal littermate rats and eliminated the infection within 3 days. In vivo depletion of NK cells, or NK subpopulations expressing Ly49 receptors, increased the bacterial load in the spleen, indicating that these cells we...

Short-term Administration of Ethanol in Mice Deviates Antigen Presentation Activity Towards B Cells

Scandinavian Journal of Immunology — Sun, 14 Jun 2009 23:00:00 +0100

Alcohol has a variety of short- and long-term effects on cell-mediated and humoral immune response. Herein, we have characterized the impact of high-dose EtOH administration on phenotypic and functional features of murine APC subsets, including dendritic cell (DC), macrophages and B cells. Impaired cytokine synthesis and Leishmania-phagocytosis was observed in peritoneal macrophages following EtOH administration. Moreover, EtOH exposure led to decreased levels of splenic myeloid DC and increased percentage of macrophages with no changes in splenic lymphoid DC and B cells. Adverse effects of short-term EtOH administration also resulted in impaired OVA-endocytosis by DC and macrophages. In contrast, EtOH consumption upregulates OVA-internalization by B cells. These changes on APC hierarchy m...

On the Critique by Colin Anderson of 'A Reply to Dembic: On an End to the Beginning of Mis-Understanding the Immune Response'

Scandinavian Journal of Immunology — Sun, 14 Jun 2009 20:09:00 +0100

My proposal of a set of postulates that can be used to guide computer modeling has understandably met with significant criticism at two levels, semantic and conceptual. The major source of contention is my assumption that the sorting of the paratopic repertoire is both necessary and sufficient to explain the evolutionarily selected mechanism for the self-nonself discrimination. While `necessary' is agreed upon, `sufficient' is debatable as this commentary illustrates. My essay is in defense of `sufficiency'. (Source: Scandinavian Journal of Immunology)

Expression of CD4 on Epstein–Barr Virus-immortalized B Cells

Scandinavian Journal of Immunology — Mon, 08 Jun 2009 23:00:00 +0100

Human antigen presenting cells commonly express CD4 but the significance of this phenomenon has not been clarified. We analyzed a panel of Epstein[ndash]Barr virus-immortalized B cells (so called lymphoblastoid cell lines, LCL) by using flow cytometry, DNA-microarray analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR). The number of CD4+ cells varied from cell line to cell line but expression of CD4 was detected by flow cytometry and RT-PCR in all investigated cell lines. To characterize CD4 expressing LCL in more detail, we separated CD4+ and CD4[minus] cells from single cell lines by using immunomagnetic beads. When we cultured sorted CD4+ and CD4[minus] cells, we observed that CD4 expression was stable for several passages. However, the number of CD4+ cells decreased ...

CD25 Blockade protects T Cells from Activation-induced Cell Death (AICD) via Maintenance of TOSO Expression

Scandinavian Journal of Immunology — Mon, 08 Jun 2009 23:00:00 +0100

In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti-CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT-3 together with recombinant IL-2 in the absence or presence of anti-CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). Anti-CD25 treatment inhibited several genes typically expressed during T-cell activation including granzyme B, signalling lymphocyte activation molecule, family member 1 (SLAMF1), CD40-Ligand (CD40-L), IL-9 and interferon (IFN)-[gamma]. Interestingly, anti-CD25 mAb also blocked the expression of several genes important for susceptibility to apoptosis, such as death receptor 6 (DR6) or reversed ...

Frontiers in Clinical Immunology 2008

Scandinavian Journal of Immunology — Mon, 08 Jun 2009 23:00:00 +0100

In recent years, investigations in immunology have led to progress in clinical medicine, including understanding transplant rejection, autoimmune diseases, immune deficiencies, inflammation, transplantation, cancer and the development of new vaccines. At a meeting recently held on the Mediterranean shore, advances in several facets of clinical immunology were the focus of discussion. Here, we highlight some of the debates that reflected advances in a variety of human immune disorders. (Source: Scandinavian Journal of Immunology)

The Expression of CD68 in Human Umbilical Cord Mesenchymal Stem Cells: New Evidences of Presence in Non-Myeloid Cell Types

Scandinavian Journal of Immunology — Mon, 08 Jun 2009 23:00:00 +0100

(Source: Scandinavian Journal of Immunology)

Influence of Maternal Hyperglycaemia on Cord Blood Mononuclear Cells in Response to Diabetes-associated Autoantigens

Scandinavian Journal of Immunology — Mon, 08 Jun 2009 23:00:00 +0100

This study aimed to analyze the effect of maternal hyperglycaemia on newborns with focus on the response to diabetes-associated autoantigens. Populations: (1) Newborns of T1D mothers split into groups according to maternal diabetes compensation during the 3rd trimester: perfect (n = 15) or acceptable (n = 25) compensation. (2) newborns with T1D father (n = 12) (3) newborns with a mother treated for either gestational or type 2 diabetes (n = 10) (4) control newborns (n = 25). Spontaneous as well as diabetes-associated autoantigen-stimulated production of 23 cytokines and chemokines were tested using protein microarray. In addition, the influence of glucose on cytokine and chemokine responsiveness was analyzed in vitro. The study groups differed in their spontaneous as well as stimulated cyt...

T-Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

Scandinavian Journal of Immunology — Mon, 08 Jun 2009 23:00:00 +0100

We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-[gamma] secreting cells were detected by ELISPOT. The peptides OspA17[ndash]36, OspA49[ndash]68, OspA105[ndash]124, OspA137[ndash]156, OspA193[ndash]212 and OspA233[ndash]252 showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.00...

Sera from Patients with Type 2 Diabetes Contain Agonistic Autoantibodies Against G Protein-Coupled Receptors

Scandinavian Journal of Immunology — Fri, 15 May 2009 23:00:00 +0100

(Source: Scandinavian Journal of Immunology)

Efficient Recovery of HLA Class I Expression in Human Tumor Cells After Beta2-Microglobulin Gene Transfer Using Adenoviral Vector: Implications for Cancer Immunotherapy

Scandinavian Journal of Immunology — Fri, 15 May 2009 23:00:00 +0100

In this report we characterize the newly generated adenoviral vector AdCMV[beta]2m and demonstrate an efficient [beta]2m gene transfer in tumour cell lines of different histological origin, including melanoma, prostate and colorectal carcinoma. The [beta]2m re-expression lasted for an extended period of time both in vitro and in vivo in human tumour xenograft transplants. We propose that in a subset of cancer patients with structural defect in [beta]2m gene or chromosome 15, the adenoviral-mediated recovery (or even increase) of HLA class I expression on tumour cells in combination with vaccination or adoptive T-cell therapy can provide a complementary approach to improve the clinical efficacy of cancer immunotherapy. (Source: Scandinavian Journal of Immunology)

Modelling of Bet v 1 Binding to Lipids

Scandinavian Journal of Immunology — Fri, 15 May 2009 23:00:00 +0100

As birch pollen allergen enters epithelium of allergic patients via lipid rafts and caveola we began to analyse its putative amphiphilic and lipid ligands on atomic level using molecular modelling and computational ligand docking. We carry out 3D modelling docking with both experimentally verified Bet v 1 ligands as well as larger lipid molecules for which experimental affinity studies were not available. The results suggest that the hydrophobic cavity of Bet v 1 has different binding sites for different ligands and groups of ligand type-specific amino acids can be defined. Bet v 1 proteins may also be able to bind and transport more complex amphiphilic molecules like ceramides and sphingomyelins known to be enriched on caveolae/lipid rafts. Furthermore, the suggested binding mode, where t...

The Role of Granulocyte Macrophage-Colony Stimulating Factor in Gastrointestinal Immunity to Salmonellosis

Scandinavian Journal of Immunology — Fri, 15 May 2009 23:00:00 +0100

Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF[minus]/[minus] mice. Furthermore, GM-CSF[minus]/[minus] mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a ...

Impact of Platelets and Fresh Frozen Plasma in Contrast to Red Cell Concentrate on Unstimulated and Stimulated Cytokine Release in an In Vitro Model of Transfusion

Scandinavian Journal of Immunology — Fri, 15 May 2009 23:00:00 +0100

Transfusion of blood may contribute to immunomodulation. Leuco-depleted standard blood products are supposed to result in less immunomodulation compared with whole blood. To determine the influence of leuco-depleted blood products on the cytokine response, red blood cell concentrates (RBC), fresh frozen plasma (FFP) and platelet concentrates (PC) were investigated in an in vitro model of blood transfusion. Leuco-depleted standard blood bank RBC, FFP and PC were mixed in vitro with AB0 compatible venous blood from healthy volunteers in ratios of 3:1, 1:1 and 1:3. Specimens were incubated in presence or absence of lipopolysaccharide, 1 [mu]g/ml. After 24 h of incubation cytokine release of tumour necrosis factor (TNF)-[alpha] and interleukin-10 (IL-10) was measured in cell culture supernatan...

Is the Dust Mite Allergen Der p1 Protozoal in Origin?

Scandinavian Journal of Immunology — Sat, 25 Apr 2009 04:00:00 +0100

(Source: Scandinavian Journal of Immunology)

Variants of the IL23R Gene are Associated with Ankylosing Spondylitis but not with Sjögren Syndrome in Hungarian Population Samples

Scandinavian Journal of Immunology — Sat, 25 Apr 2009 04:00:00 +0100

In conclusion, we confirmed the susceptibility or protective associations of IL23R polymorphisms with AS in a Hungarian population and first demonstrated the involvement of the rs11805303 intronic single nucleotide polymorphisms, which was tested so far only for other autoimmune diseases. (Source: Scandinavian Journal of Immunology)

Suppression of Lymphocyte Proliferation and Regulation of Dendritic Cell Phenotype by Soluble Mediators from Rat Lacrimal Epithelial Cells

Scandinavian Journal of Immunology — Sat, 25 Apr 2009 04:00:00 +0100

Lacrimal epithelial cells appear to constitutively secrete autoantigens to their underling stroma. The present experiments address the hypothesis that they also secrete soluble factors that regulate immune responses. Epithelial cells, spleen cells and lymphocytes were obtained from rabbits or rats and cultured in various configurations. Monocytes from rat bone marrow were matured to dendritic cells (DC) ex vivo. Proliferation was measured by [3H]-thymidine incorporation; surface MHC Class II and CD86 using flow cytometry; and mRNA relative abundances using real time RT-PCR. Microporous culture inserts containing rat lacrimal cells inhibited proliferation of rabbit lymphocytes co-cultured with autologous lacrimal cells and of rat lymphocytes co-cultured with TNF-[alpha]-stimulated DC. They ...

Vaccination with β2-Microglobulin-Deficient Dendritic Cells Protects Against Growth of β2-Microglobulin-Deficient Tumours

Scandinavian Journal of Immunology — Sat, 25 Apr 2009 04:00:00 +0100

In this study, we demonstrate enhanced in vivo protection against growth of [beta]2-microglobulin-deficient tumour cells in syngeneic C57Bl/6 mice, following vaccination with [beta]2-microglobulin-deficient dendritic cells. In vitro analysis suggested that vaccinated mice produced CD3+ cells, which could induce apoptosis in syngeneic [beta]2-microglobulin-deficient tumour and non-malignant cells. Further investigation of target cell recognition suggested that also tumour cells lacking expression of classical major histocompatibility complex class I heavy chains and functional transporter associated with antigen processing molecules were recognized by CD3+ effector cells from vaccinated mice. Histopathological examination of organs from vaccinated mice showed no significant vaccination-indu...

CD25 Shedding by Human Natural Occurring CD4+CD25+ Regulatory T Cells does not Inhibit the Action of IL-2

Scandinavian Journal of Immunology — Sat, 25 Apr 2009 04:00:00 +0100

Regulatory T (Treg) cells are important for the maintenance of peripheral tolerance and inhibition of pathogenic T-cell responses. Therefore, they are important for the limitation of chronic inflammation but can also be deleterious by e.g. limiting antitumour immune responses. Natural occurring Tregs are known to inhibit CD4+ T cell in a contact-dependent manner, but at the same time, various suppressive factors are secreted. We, here, demonstrate that human naturally occurring CD4+CD25+ Tregs are able to shed large amounts of soluble CD25 upon activation. Secretion of sCD25 could add to the inhibitory effect of Tregs as such secretion in other settings has been proposed to act as a sink for local IL-2. However, we here demonstrate that supernatant from human Tregs containing high concentr...

Effects of CD14, TLR2, TLR4, LPB, and IL-6 Gene Polymorphisms on Chlamydia pneumoniae Growth in Human Macrophages In Vitro

Scandinavian Journal of Immunology — Sat, 25 Apr 2009 04:00:00 +0100

In this study, we evaluated the effects of innate immunity genes CD14 [minus]260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL6 [minus]174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 [minus]260 C>T TT genotype cells and the difference to CC and CT genotypes was statistically significant (P = 0.032 and 0.022 respectively). The G-allele of the IL6 [minus]174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes (P = 0.018). TLR2 Arg 753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth. (Source: Scandinavian Journal of Immunology)

Increase in Human Endogenous Retrovirus HERV-K (HML-2) Viral Load in Active Rheumatoid Arthritis

Scandinavian Journal of Immunology — Fri, 24 Apr 2009 23:00:00 +0100

To study the viral loads of human endogenous retrovirus HERV-K (HML-2) type 1 and type 2 in rheumatoid arthritis (RA), we measured the viral loads of HERV-K (HML-2) type 1 and type 2 using nucleic acid sequence-based amplification (NASBA) technology. We analyzed plasma samples from RA patients (n = 79) and healthy volunteers (HV, n = 46) and synovial fluid samples from RA (n = 10) and osteoarthritis (OA, n = 10) patients. HERV-K type 1 and type 2 viruses were detected and quantified for the majority of plasma and synovial fluid samples from RA patients. HERV-K type 1 and type 2 viral loads were significantly elevated in RA patients compared with HV in plasma (P < 0.0001) and from RA patients compared with OA patients in synovial fluid (type 1: P = 0.0007; type 2: P = 0.023). Moreover, an a...

Cell Specific Synovial Expression of Nicotinic Alpha 7 Acetylcholine Receptor in Rheumatoid Arthritis and Psoriatic Arthritis

Scandinavian Journal of Immunology — Fri, 24 Apr 2009 23:00:00 +0100

Neuroimmune interactions are known to influence several chronic inflammatory and rheumatic diseases, but the underlying mechanisms have been insufficiently elucidated. The cholinergic anti-inflammatory pathway is characterized by neural regulation of systemic inflammation, mediated by the vagus nerve and specific cholinergic stimulation of the nicotinic [alpha]-7 acetylcholine receptor ([alpha]7nAChR) on immune cells. Moreover, [alpha]7nAChR has been shown important for immune regulation also in the absence of nerves, but little is known about these mechanisms in chronic joint inflammation. The expression and localization of [alpha]7nAChR in synovial biopsies from patients with rheumatoid arthritis and psoriatic arthritis was investigated by immunohistochemistry using monoclonal antibody a...

Antibodies against a Class II HLA–Peptide Complex Raised by Active Immunization of Mice with Antigen Mimicking Peptides

Scandinavian Journal of Immunology — Fri, 24 Apr 2009 23:00:00 +0100

Multiple sclerosis (MS) is an autoimmune disease linked to the human leucocyte antigen (HLA) class II genes DRB1*1501, DRB5*0101 and DQB1*0602. T cells reactive towards the DRB1*1501 in complex with various peptides derived from myelin basic protein (MBP), which is the major component of myelin, have been found in the peripheral blood of MS patients. These autoreactive T cells are believed to play a role in the pathogenesis of MS. In this article, antibodies against the HLA complex DR2b (DRA1*0101/DRB1*1501) in complex with the MBP-derived peptide MBP85-99 have been generated by immunization of NMRI mice with three different antigen mimicking peptides displayed on M13 bacteriophages. The peptides mimick the epitope of a monoclonal antibody specific for the DR2b[ndash]MBP85-99 complex. The ...

Development of an Effective Method for Dendritic Cell Immunotherapy of Mouse Melanoma

Scandinavian Journal of Immunology — Fri, 24 Apr 2009 23:00:00 +0100

Dendritic cell (DC) immunotherapy is a strong candidate for the treatment of incurable cancers especially malignant melanoma. Nevertheless, the proper guideline of DC immunotherapy does not exist. The absence of the guideline is also an obstacle to clinical trials of DC immunotherapy. So we conducted this study in order to develop an effective DC preparation method for immunotherapy in mouse malignant melanoma. Mouse bone marrow-derived DC were stimulated with tumour antigen alone or tumour antigen plus a cocktail (anti-CD40 antibody +TNF-[alpha]+ IL-1[beta]) for 8, 24 or 48 h and the characteristics of these DC, such as surface molecules (CD40, CD80, CD86, MHC class II, CCR7), cytokines(IL-12, IFN-[gamma], and IL-10), DC-induced T cell proliferation in vitro, and the production of IFN-[ga...

Association between Asymmetric Dimethylarginine and Neopterin in Patients with and without Angiographic Coronary Artery Disease

Scandinavian Journal of Immunology — Wed, 08 Apr 2009 04:00:00 +0100

In conclusion, increased ADMA concentrations in patients at risk for atherosclerosis are associated with increased neopterin concentrations. Data suggest that immune activation may contribute to increased ADMA production in CAD patients. (Source: Scandinavian Journal of Immunology)

Immunological Determinants in a Mouse Model of Chemical-Induced Asthma After Multiple Exposures

Scandinavian Journal of Immunology — Wed, 08 Apr 2009 04:00:00 +0100

In a mouse model of chemical-induced asthma, we investigated the effects of multiple challenges, using toluene diisocyanate (TDI), a known cause of occupational asthma. On days 1 and 7, BALB/c mice received TDI or vehicle (acetone/olive oil). On days 10, 13 and 16 the mice received an intranasal instillation of TDI. Ventilatory function (Penh) was monitored by whole body plethysmography for 40 min after each challenge. Reactivity to methacholine was measured 22 h later. Pulmonary inflammation, TNF-[alpha] and MIP-2 levels were assessed 24 h after the last challenge by broncho-alveolar lavage (BAL). Other immunological parameters included total IgE, lymphocyte sub-populations in auricular and cervical lymph nodes, and IL-4, IFN-[gamma] and IL-13 levels in supernatants of lymph node cells, c...

Functionally Active Toll-Like Receptor 3 on Human Primary and Metastatic Cancer Cells

Scandinavian Journal of Immunology — Wed, 08 Apr 2009 04:00:00 +0100

Toll-like receptor 3 (TLR3) is a member of Toll-like receptors who recognize structurally conserved molecules derived from pathogens and trigger the immune response. To clarify if TLR3, is expressed in certain tumour cell lines and whether it is functional and what is the response of these cell lines to different concentrations of poly I:C treatment, we have screened SW480, SW620, FaDu and Detroit 562 cell lines using real-time PCR, flow cytometry and ELISA. We have shown that all these cell lines express TLR3 on mRNA and protein level but it is only functional in Detroit 562 cell line since only in these cells poly I:C treatment triggered the IL-6 secretion. In addition, poly I:C treatment inhibited cell growth and triggered up-regulation of IL-12p40, IL-8 and Il-1[alpha] in Detroit 562 c...

Influence of Tumour Condition on the Macrophage Activity in Candida albicans Infection

Scandinavian Journal of Immunology — Wed, 08 Apr 2009 04:00:00 +0100

To better understand the interactions between opportunistic fungi and their hosts, we investigated hydrogen peroxide (H2O2), nitric oxide and TNF-[alpha] production by peritoneal macrophages from Ehrlich tumour-bearing mice (TBM) during microbial infections. For this purpose, TBM at days 7, 14 and 21 of tumour progression were inoculated intraperitoneally with C. albicans and evaluated after 24 and 72 h. We observed that TBM showed significant increases in H2O2, TNF-[alpha] levels and fungal clearance at day 7 after C. albicans infection. However, as the tumour advanced, there was a progressive decline in the release of H2O2 and TNF-[alpha] that was paired with the dissemination of C. albicans. These results demonstrate that protective macrophage activities against Candida albicans are lim...

Immune and nervous systems share molecular and functional similarities: memory storage mechanism.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:55:37 +0100

Authors: Habibi L, Ebtekar M, Jameie SB One of the most complex and important features of both the nervous and immune systems is their data storage and retrieval capability. Both systems encounter a common and complex challenge on how to overcome the cumbersome task of data management. Because each neuron makes many synapses with other neurons, they are capable of receiving data from thousands of synaptic connections. The immune system B and T cells have to deal with a similar level of complexity because of their unlimited task of recognizing foreign antigens. As for the complexity of memory storage, it has been proposed that both systems may share a common set of molecular mechanisms. Here, we review the molecular bases of memory storage in neurons and immune cells based on recent stu...

A reply to Dembic: on an end to the beginning of misunderstanding the immune response.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:55:32 +0100

Authors: Cohn M We all agree that dealing with the complexity and volume of the data necessitates the use of computer modelling. This in turn requires a heuristic conceptual framework to guide this modelling. The first attempt to do this by Cohn has been criticized by Dembic as being severely lacking. This commentary deals with his criticism of the framework to show why Cohn's postulates, in fact, remain unchallenged. PMID: 19284493 [PubMed - in process] (Source: Scandinavian Journal of Immunology)

Placing regulatory T cells into global theories of immunity: an analysis of Cohn's challenge to integrity (Dembic).

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:55:28 +0100

Authors: Anderson CC In broadening the integrity model, Zlatko Dembic provided one of the few plausible explanations for the existence of regulatory T cells that has been postulated to date and at the same time highlighted deficiencies of the associative antigen recognition model. In defending the virtues of associative antigen recognition, Melvin Cohn has challenged the integrity model and the concept that regulatory T cells have a role in defining the specificity of immune responses. The critique of Cohn's analysis I present here suggests that a greater consideration of quantitative evolutionary constraints removes most of the challenges to integrity. PMID: 19284494 [PubMed - in process] (Source: Scandinavian Journal of Immunology)

Susceptibility to Yersinia pseudotuberculosis infection is linked to the pattern of macrophage activation.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:55:24 +0100

In this study, the pattern of macrophage activation in Y. pseudotuberculosis-infected BALB/c (Yersinia-susceptible) and C57BL/6 (Yersinia-resistant) mice and their immunostimulatory capacity were analysed. In the early phase of infection, macrophages obtained from C57BL/6 mice produced higher levels of NO, lower arginase activity, and larger amounts of IL-12 and TNF-alpha than macrophages from BALB/c mice. On the other hand, macrophages derived from BALB/c mice produced higher levels of IL-10 and TGF-beta than C57BL/6 mice. The Y. pseudotuberculosis infection leads to a fall in the macrophage immunostimulatory capacity of both strains of mice, with T-cell proliferation significantly reduced 12 h after infection. Moreover, we observed in the supernatant of co-culture of macrophages from inf...

Dendritic cells engineered to express defined allo-HLA peptide complexes induce antigen-specific cytotoxic T cells efficiently killing tumour cells.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:55:17 +0100

Authors: Stronen E, Abrahamsen IW, Gaudernack G, Wälchli S, Munthe E, Buus S, Johansen FE, Lund-Johansen F, Olweus J Most tumour-associated antigens (TAA) are non-mutated self-antigens. The peripheral T cell repertoire is devoid of high-avidity TAA-specific cytotoxic T lymphocytes (CTL) due to self-tolerance. As tolerance is major histocompatibility complex-restricted, T cells may be immunized against TAA presented by a non-self human leucocyte antigen (HLA) molecule and transferred to cancer patients expressing that HLA molecule. Obtaining allo-restricted CTL of high-avidity and low cross-reactivity has, however, proven difficult. Here, we show that dendritic cells transfected with mRNA encoding HLA-A*0201, efficiently present externally loaded peptides from the antigen, Melan-A/...

Induction of TLR tolerance in human macrophages by adiponectin: does LPS play a role?

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:55:02 +0100

Authors: Turner JJ, Smolinska MJ, Sacre SM, Foxwell BM Obesity is regarded as a pro-inflammatory state. It is associated with low circulating levels of the adipokine, adiponectin, which is considered to be an anti-inflammatory. However, adiponectin knockout mice do not consistently demonstrate pro-inflammatory phenotypes, suggesting more complexity in the in vivo immunomodulatory effects of adiponectin than originally anticipated. Moreover, adiponectin exerts pro-inflammatory effects in some experimental systems. This contradiction has been resolved by hypothesizing that adiponectin induces tolerance to inflammatory stimuli, notably Toll-like receptor (TLR) ligands. We noticed that this effect resembled lipopolysaccharide (LPS) tolerance and therefore tested adiponectin from a variety ...

Activated T cells inhibit NK cell-mediated tumour rejection.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:54:49 +0100

Authors: Wang XJ, Hu J, Yuan J, Peng YM, Gui L, He WF, Tan J, Luo GX, Wu J Previous studies have described the regulation of some T-cell subsets toward natural killer (NK) cells. Naturally occurring CD4(+)CD25(+) T regulatory cells can inhibit NK cell cytotoxicity, while activated interleukin-2 (IL-2) secreting T cells can stimulate NK cells. However, little is known about the impact of the integrity T-cell population on the final outcome of NK cell cytotoxicity. We thus examined the possible role of activated T cells in affecting NK cell cytotoxicity by mixed lymphocyte co-cultures in vitro and a B16 melanoma tumour model in vivo. In our study, activated T cells were found to be able to significantly inhibit NK cell cytotoxicity in vitro and blunt NK cell-mediated tumour rejection in ...

More vaccine efficacy studies on the recombinant Bacille Calmette-Guerin co-expressing Ag85B, Mpt64 and Mtb8.4.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:54:32 +0100

Authors: Qie YQ, Wang JL, Liu W, Shen H, Chen JZ, Zhu BD, Xu Y, Zhang XL, Wang HH The immunogenicity of the recombinant Bacille Calmette-Guerin: rBCG-Ag85B-Mpt64(190-198)-Mtb8.4 (rBCG-AMM) was evaluated in our previous study. This paper compares the protective efficacy of rBCG-AMM, rBCG-A which overexpresses Ag85B and BCG in C57BL/6 mice. There was no significant difference in proliferation characteristics among rBCG-AMM, rBCG-A and BCG. The growth characteristics of rBCG-AMM in host tissue were identical to control BCG, suggesting the improved protective efficacy was directly related to the expression of the Ag85B-Mpt64(190-198)-Mtb8.4 fusion protein. The protective experiment demonstrated that rBCG-AMM could confer similar or even better protective efficacy against Mycobacterium tube...

Differential activation of dendritic cells by Toll-like receptor agonists isolated from the Gram-positive vaccine vector Streptococcus gordonii.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:54:20 +0100

Authors: Mayer ML, Phillips CM, Townsend RA, Halperin SA, Lee SF The oral commensal bacterium Streptococcus gordonii has been gathering interest as a candidate live mucosal vaccine delivery vector. S. gordonii has been shown to be capable of activating antigen presenting immune cells in a manner which leads to their activation and maturation, yet the mechanism used by S. gordonii to do so is poorly understood. The aim of this work was to investigate the immunostimulatory components of S. gordonii in inducing murine dendritic cell (DC) activation and maturation. Lipoteichoic acid (LTA), lipoprotein (LP), peptidoglycan (PGN), and DNA were isolated from S. gordonii, and used to stimulate murine DC. Cytokine production and DC surface marker upregulation in response to the bacterial compone...

Transcriptional profiles in urine during acute rejection, bacteriuria, CMV infection and stable graft function after renal transplantation.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:54:12 +0100

Authors: Øzbay A, Tørring C, Olsen R, Carstens J Acute rejection remains an important cause of renal allograft dysfunction and the need for accurate diagnosis is essential to treat transplant recipients successfully. Molecular markers in urine may serve as a diagnostic tool in acute rejection, but controversy still exists regarding the uniqueness of these biomarkers. We measured mRNA of perforin (PRF), granzyme B (GZMB) and granulysin (GNLY) normalized to cyclophilin B in urine specimens from 24 renal allograft recipients with acute rejection, 12 with bacteriuria, 11 with cytomegalovirus (CMV) infections and 17 controls with stable graft function. Measurements were performed using a real-time polymerase chain reaction assay. mRNA levels (means [95% CI]) for all three markers ...

Absence of tyrosinase-related protein-2/dopachrome tautomerase transcripts in PBMCs from vitiligo patients.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:54:07 +0100

Authors: Bam M, Bagchi T Tolerance is achieved by mechanisms occurring in both the thymus and periphery. Several reports have shown that presence of an antigen in the peripheral circulation results in tolerance induction. These reports imply that absence of a self-antigen can lead to induction of autoimmunity. Here, we show that tyrosinase-related protein 2 (TRP-2) transcript is not detected in the peripheral blood mononuclear cells (PBMC) of vitiligo patients but is detected in healthy controls. Our result indicates that probably due to lack of expression in the PBMC, TRP-2 is not available for induction and maintenance of peripheral tolerance in vitiligo patients. It is also reported by others that co-stimulatory molecules are required for the initiation of autoimmune diseases in exp...

Complement inhibitor C4b-binding protein in primary Sjögren's syndrome and its association with other disease markers.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:53:56 +0100

In conclusion, C4BP levels are increased in patients suffering from pSS proportional to their acute phase response. However, in the most active cases, with the most widespread autoantibody production, C4BP levels were decreased in parallel with levels of C3 and C4 and CD4+ T cells, suggesting that disturbed complement regulation may contribute to pathogenicity in pSS. PMID: 19284503 [PubMed - in process] (Source: Scandinavian Journal of Immunology)

Eosinophil cationic protein stimulates migration of human lung fibroblasts in vitro.

Scandinavian Journal of Immunology — Fri, 20 Mar 2009 06:48:44 +0100

Authors: Zagai U, Lundahl J, Klominek J, Venge P, Sköld CM Asthma is characterized by eosinophilic inflammation and remodelling of the airways. Eosinophil cationic protein (ECP) is a protein released by activated eosinophils and the hypothesis that ECP contributes to the development of structural changes in the airways of asthmatics has been posed. Fibroblast recruitment is an important step in the remodelling process, and we therefore put the question whether ECP stimulates migration of human lung fibroblasts. Human peripheral eosinophils isolated from buffycoats from healthy individuals were cultured and conditioned media (CM) were collected. Native ECP was extracted from human peripheral eosinophils by gel filtration, ion-exchange and chelating chromatography. The ability of eo...

Effect of Vibrio cholerae on chemokine gene expression in HT29 cells and its modulation by Lactobacillus GG.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

This study examined the effect of Vibrio cholerae and Lactobacillus rhamnosus GG on inflammatory chemokine gene expression in the HT29 human intestinal epithelial cell line. HT29 cells were exposed to V. cholerae 0139, Lactobacillus or both for 2 h and cultured further thereafter for 4 h. RNA was extracted from the cells and expression of genes for chemokines and related molecules was quantitated by real time PCR using a pathway-focused PCR array. TLR4 was silenced using shRNA and output of interleukin-8 (IL-8) into the media quantitated with and without V. cholerae exposure. NFkappaB and p38 MAP kinase activation were determined by immunoblotting for IkappaBalpha and phosphorylated p38. Vibrio cholerae significantly upregulated gene expression for the neutrophil chemoattractant CXCL chemo...

Highly arthritis-susceptible DA rats express IL-1beta in articular cartilage.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Weiss RJ, Erlandsson Harris H, Palmblad K There are genetically determined differences in susceptibility to arthritis among inbred rat strains. The aim of the present study was to elucidate phenotypical differences, by determining expression of TNF and IL-1beta, two pivotal mediators of arthritis, in the highly arthritis-prone Dark Agouti (DA) rat compared to that of two arthritis-resistant rat strains, the major histocompatibility complex-homologous Piebald-Viral-Glaxo (PVG.1AV1) rat and the Brown Norway (BN) rat, assessed by immunohistochemistry. We demonstrate a distinct difference in articular cartilage, with chondrocytes expressing IL-1beta, not TNF, in the highly arthritis-prone DA rat as opposed to the two arthritis-resistant BN or PVG.1AV1 rat strains, where no cytokin...

IC31, a two-component novel adjuvant mixed with a conjugate vaccine enhances protective immunity against pneumococcal disease in neonatal mice.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Olafsdottir TA, Lingnau K, Nagy E, Jonsdottir I IC31 is a novel adjuvant which combines the immunostimulatory effects of an 11-mer antibacterial peptide (KLKL(5)KLK) and a synthetic oligodeoxynucleotide (ODN1a) which is a Toll-like receptor 9 agonist without containing cytosine phosphate guanine (CpG) motifs. The effects of IC31 on neonatal immune response to vaccination have not been reported. Neonatal mice were immunized once or twice with a Streptococcus pneumoniae serotype 1 polysaccharide conjugate containing Tetanus Toxoid (Pnc1-TT) carrier protein, with or without IC31 or CpG-ODN. IC31 significantly enhanced IgG1, IgG2a and IgG2b antibodies (Ab) to the serotype 1 polysaccharide. One dose of Pnc1-TT and low dose IC31 elicited high Ab levels that protected the neonatal mi...

Modified human beta 2-microglobulin (desLys(58)) displays decreased affinity for the heavy chain of MHC class I and induces nitric oxide production and apoptosis.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

In conclusion, these data show that dbeta2m is not able to support the formation of a stable tri-molecular MHC-I complex at physiological temperature and that dbeta2m exerts other biological functions compared to beta2m when bound to cells. PMID: 19281532 [PubMed - in process] (Source: Scandinavian Journal of Immunology)

Th1 cell reactivity and HLA-DR binding prediction for promiscuous recognition of MPT63 (Rv1926c), a major secreted protein of Mycobacterium tuberculosis.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

This study was undertaken to determine the reactivity of MPT63 in T helper 1 (Th1) cell assays, i.e. antigen-induced proliferation and interferon-gamma secretion, using peripheral blood mononuclear cells (PBMCs) obtained from 72 Mycobacterium bovis Bacille Calmette-Guérin vaccinated healthy subjects. PBMCs were tested with complex mycobacterial antigens and pools of synthetic peptides corresponding to MPT63, MPB70, MT24, PPE68, CFP10 and ESAT-6. The results showed that MPT63 induced moderate Th1 cell reactivity which was equivalent to the reactivity induced by other secreted antigens of M. tuberculosis, i.e. MT24 and MPB70. Furthermore, human leucocyte antigen (HLA) heterogeneity of the responding donors suggested that MPT63 was presented to Th1 cells promiscuously. Analysis of the MP...

Effects of human fecal flora on intestinal morphology and mucosal immunity in human flora-associated piglet.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

This study confirms that the composition of gut microbes differentially affects the host intestinal mucosal immunity and suggests that commensal bacteria have great effects on intestinal health and development. PMID: 19281534 [PubMed - in process] (Source: Scandinavian Journal of Immunology)

Effects of haemofiltration and mannitol treatment on cardiopulmonary-bypass induced immunosuppression.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

This study shows that the suppression of the stimulated immune response after CPB can potentially be alleviated by mannitol or haemofiltration in an experimental in-vitro setting. In the light of data showing that this depression of the immune response might affect the post-operative course of patients, these results could have a potential clinical relevance. PMID: 19281535 [PubMed - in process] (Source: Scandinavian Journal of Immunology)

Effect of an extract based on the medicinal mushroom Agaricus blazei murill on release of cytokines, chemokines and leukocyte growth factors in human blood ex vivo and in vivo.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Johnson E, Førland DT, Saetre L, Bernardshaw SV, Lyberg T, Hetland G An immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro-inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)-2, interferon (IFN)-gamma and IL-12], T helper 2 cytokines (IL-4, IL-5 and IL-13), pleiotropic (IL-7, IL-17), pro-inflammatory [IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha (mainly...

An alkaloid extract of evanta, traditionally used as anti-leishmania agent in Bolivia, inhibits cellular proliferation and interferon-gamma production in polyclonally activated cells.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Calla-Magarinos J, Giménez A, Troye-Blomberg M, Fernández C Traditional medicine and scientific studies have shown that the raw extract of Evanta [Galipea longiflora, Angostura longiflora (Krause) Kallunki] exhibits anti-leishmanial activity. We hypothesized that the healing observed when using this plant might not only be due to the direct action on the parasite, but possibly to a parallel effect on the host immune response to the parasite involved in the healing process. We show here that an alkaloid extract of Evanta (AEE) directly killed the parasite already at a dose of 10 microg/ml, but at this low concentration, AEE did not have a major effect on viability and proliferation of eukaryotic cells. The whole extract was also found to be stronger than 2-phenylquino...

Relationship between circulating levels of IFN-gamma, IL-10, CXCL9 and CCL2 in pulmonary and extrapulmonary tuberculosis is dependent on disease severity.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Hasan Z, Jamil B, Khan J, Ali R, Khan MA, Nasir N, Yusuf MS, Jamil S, Irfan M, Hussain R Protection against Mycobacterium tuberculosis infection is dependent on T cell and macrophage activation regulated by cytokines. Cytokines and chemokines produced at disease sites may be released into circulation. Data available on circulating cytokines in tuberculosis (TB) is mostly on pulmonary TB (PTB) with limited information on extrapulmonary disease (EPul-TB). We measured interferon-gamma (IFN-gamma), interkeukin-10 (IL-10), CXCL9 and CCL2 in sera of patients (n = 80) including; PTB (n = 42), EPul-TB (n = 38) and BCG vaccinated healthy endemic controls (EC, n = 42). EPul-TB patients comprised those with less severe (LNTB) or severe (SevTB) disease. Serum IFN-gamma, IL-10 and CXCL9 le...

Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Vasakova M, Sterclova M, Kolesar L, Slavcev A, Pohunek P, Sulc J, Skibova J, Striz I Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and sarcoidosis belong to interstitial lung diseases (ILD) where an imbalance of regulatory, profibrotic and antifibrotic cytokines is hypothesized. The relationship of bronchoalveolar lavage (BAL) fluid (BALF) cytokines, BALF cell profile and ILD course is supposed. The aim of our study was to correlate BALF cytokine and chemokine levels with BALF cellular characteristics and lung function parameters in different ILD. Twenty-two sarcoidosis, seven IPF and 11 HP patients underwent lung function tests and BAL. The BALF differential cell counts and superficial cell markers were characterized, and MCP-1, MIP-1alpha, MIP-1beta,...

Natural immunity has significant impact on immune responses against cancer.

Scandinavian Journal of Immunology — Sun, 01 Mar 2009 05:00:00 +0100

Authors: Rubin B The immune system defends the host against pathogenic attacks by micro-organisms and their products. It does not react against self-components due to the relatively efficient negative selection of developing T lymphocytes in the thymus. This process does permit T cells with low avidity against self to be present in the T cell repertoire. Such cells play an important physiological role as the host needs so-called autoimmune reactions in order to eliminate dying cells or transformed tumour cells. One of the mysteries in immunology is how the host maintains beneficial autoimmune reactions and avoids pathogenic autoimmune reactions. Activation of the adaptive T lymphocytes is mediated by the low avidity interaction between T-cell antigen receptors and antigenic peptides as...

A novel anti-inflammatory compound, artonkin-4'-O-glucoside, from the leaves of Artocarpus tonkinensis suppresses experimentally induced arthritis.

Scandinavian Journal of Immunology — Fri, 30 Jan 2009 03:57:47 +0100

Authors: Dang DT, Eriste E, Liepinsh E, Trinh TT, Erlandsson-Harris H, Sillard R, Larsson P Artocarpus tonkinenesis (Moraceae) has been used in Vietnamese traditional medicine for the treatment of backache and joint diseases since many 100 years. We have previously shown that a crude extract of A. tonkinensis elicited anti-inflammatory effects in rat collagen-induced arthritis (CIA), with significant improvement of disease symptoms. However, the pharmacological basis of the bioactivity of A. tonkinensis extract is not known. In the present study, we have isolated four individual active components from A. tonkinensis extract by reverse phase high-pressure liquid chromatography. The structures of the compounds were determined by nuclear magnetic resonance (NMR) spectroscopy and mass spec...

Contribution of intestinal epithelial cells to innate immunity of the human gut--studies on polarized monolayers of colon carcinoma cells.

Scandinavian Journal of Immunology — Fri, 30 Jan 2009 03:57:39 +0100

Authors: Ou G, Baranov V, Lundmark E, Hammarström S, Hammarström ML The aim was to establish an in vitro model for studies of innate defence mechanisms of human intestinal epithelium. Ultrastructural characterization and determination of mRNA expression levels for apical glycocalyx and mucous components showed that polarized, tight monolayers of the colon carcinoma cell lines T84 and Caco2 acquire the features of mature- and immature columnar epithelial cells, respectively. Polarized monolayers were challenged with non-pathogenic Gram+ and Gram- bacteria from the apical side and the proinflammatory cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from the basolateral side. Immune responses were estimated as chan...

Differential Expression of Immune Genes in Atlantic Salmon (Salmo salar L.) Challenged Intraperitoneally or by Cohabitation with IPNV.

Scandinavian Journal of Immunology — Thu, 29 Jan 2009 04:33:59 +0100

Authors: Ingerslev HC, Rønneseth A, Pettersen EF, Wergeland HI Atlantic salmon smolts challenged intraperitoneally (ip) and by cohabitation with a highly virulent strain of infectious pancreatic necrosis virus showed strong activation of important immune genes in spleen, liver, head-kidney and gill measured by real-time quantitative PCR. The genes investigated were IL-1beta, IL-10, IFN-alpha, IFN-gamma, Mx, MHC-I, MHC-II, TCR-alpha, CD8-alpha and mIgM. A low final cumulative mortality of about 10% was seen in the ip-challenged group, while more than 40% of the cohabitants died in the sampling period. Sampling was performed at day 15, 24 and 37 post ip-challenge. Overall, the expression of the investigated genes varied highly. The expression of IL-1beta, IL-10, MHC-II, TCR-alpha, C...

A Novel Anti-inflammatory Compound, Artonkin-4'-O-glucoside, from the Leaves of Artocarpus tonkinensis Suppresses Experimentally Induced Arthritis*.

Scandinavian Journal of Immunology — Thu, 29 Jan 2009 04:33:45 +0100

Elevated Expression of Transmembrane IL-15 in Immune Cells Correlates with the Development of Murine Lupus: a Potential Target for Immunotherapy Against SLE.

Scandinavian Journal of Immunology — Thu, 29 Jan 2009 04:33:41 +0100

Authors: Bo H, Wei XQ, Dong H, Zhang Y, Lv P, Liu W, Koutoulaki A, Gao XM Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15Ralpha) has been suggested as the main mechanism for IL-15 anchoring to the cell surface, but it is also evident that IL-15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15) with Igkappa chain leader sequence resulted in secretion of most of the recombinant hIL-15 expressed in transfectant cells, thus identifying the transmembrane region of IL-15. A fusion protein (hIL-15Ralpha-Fc) between the extracellular domain of hIL-15Ralpha and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15 expression in ...

Contribution of intestinal epithelial cells to innate immunity of the human gut - studies on polarized monolayers of colon carcinoma cells.

Scandinavian Journal of Immunology — Thu, 29 Jan 2009 04:33:37 +0100

Molecular Characterization of Patients with X-linked Hyper-IgM Syndrome: Description of Two Novel CD40L Mutations.

Scandinavian Journal of Immunology — Thu, 29 Jan 2009 04:33:33 +0100

Authors: Rangel-Santos A, Wakim VL, Jacob CM, Pastorino AC, Cunha JM, Collanieri AC, Niemela JE, Grumach AS, Duarte AJ, Moraes-Vasconcelos D, Oliveira JB Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X m...

Activity of alpha2,6-Sialyltransferase and its Gene Expression in Peripheral B Lymphocytes in Patients with IgA Nephropathy.

Scandinavian Journal of Immunology — Thu, 29 Jan 2009 04:33:29 +0100

Authors: Ding JX, Xu LX, Zhu L, Lv JC, Zhao MH, Zhang H, Wang HY It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1 may result from changes in the activity of alpha2,6-sialyltransferase (alpha2,6-ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes. Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B lymphocytes were isolated by CD-19-positive magnetic beads. The expression level of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase polymerase chain reaction (PCR). Serum IgA1 and sialylation levels were detected by enzyme-linked immunosorbent assay (ELISA) and specific lectin-binding ELISA. Activity of alpha2...

Impact of Peroxynitrite Modification on Structure and Immunogenicity of H2A Histone.

Scandinavian Journal of Immunology — Wed, 28 Jan 2009 03:57:16 +0100

In this study, commercially available H2A histone was exposed to peroxynitrite generated in vitro. The peroxynitrite-mediated structural changes in histone were studied by ultraviolet & fluorescence spectroscopy, high performance liquid chromatography, anilinonaphthalene-8-sulfonic acid binding and polyacrylamide gel electrophoresis. Analysis of results revealed that carbonyl, nitrotyrosine and dityrosine contents were significantly increased in peroxynitrite-modified H2A compared with native H2A. Rabbits challenged with peroxynitrite-modified H2A induced high titre antibodies. The immunogenicity of peroxynitrite-modified H2A was directly proportional to protein nitrotyrosine content and induced antibodies showed specificity for the immunogen and good cross-reaction with nitrated epito...

Induction of multiepitopic and long-lasting immune responses against tumour antigens by immunization with peptides, DNA and recombinant adenoviruses expressing minigenes.

Scandinavian Journal of Immunology — Wed, 28 Jan 2009 03:57:11 +0100

In this study, with the aim of inducing multiepitopic responses against several common tumour antigens, we have designed a minigene construct encoding four human leucocyte antigen (HLA)-A2-restricted epitopes belonging to tumour antigens CEA (CEA-691 and CEA-571), MAGE2 (MAGE2-157) and MAGE3 (MAGE3-112), as well as the universal PADRE epitope recognized by T helper lymphocytes. To optimize the activation of immune responses against these epitopes, we have used different antigen formats (short peptides encompassing individual epitopes and DNA plasmids or adenoviral constructs expressing the minigene) in single or combined immunization schedules. A single immunization with either DNA plasmid or recombinant adenovirus induced a monospecific immune response against the immunodominant epitope C...

Vbeta usage and T regulatory cells in children following partial or total thymectomy after open heart surgery in infancy.

Scandinavian Journal of Immunology — Wed, 28 Jan 2009 03:57:05 +0100

Authors: Eysteinsdottir JH, Freysdottir J, Skaftadottir I, Helgason H, Haraldsson A, Ogmundsdottir HM During open heart surgery in infants the thymus was usually removed, partly or completely. Our previous studies on 16 such children indicated reduced T-cell output later in life with signs of extrathymic maturation of the T cells, but no reduction in T regulatory cells (CD4(+)CD25(+)). The diversity of the T-cell repertoire in these children was examined to test if the extrathymic microenvironment could alter Vbeta usage. The expression of Foxp3 and CD127 in CD4(+)CD25(high) T cells was measured in order to determine whether the T regulatory cells had the phenotype of natural T regulatory cells. There was a wide distribution of Vbeta usage in both study and control groups. Significant ...

Cell-Mediated Immune Responses and Protective Efficacy against Infection with Mycobacterium tuberculosis Induced by Hsp65 and hIL-2 Fusion Protein in Mice.

Scandinavian Journal of Immunology — Wed, 28 Jan 2009 03:56:56 +0100

Authors: Shi C, Yuan S, Zhang H, Zhang T, Wang L, Xu Z Heat shock protein 65 (Hsp65) is an important immunodominant antigen against tuberculosis (TB), and interleukin-2 (IL-2) plays an important role in the regulation of antimycobacteria immune responses. In order to further increase the immunogenicity of Hsp65 against infection caused by Mycobacterium tuberculosis (MTB), we expressed MTB Hsp65 and human IL-2 fusion protein, Hsp65-hIL-2, in Escherichia coli. The expression of Hsp65-hIL-2 was confirmed by Western blotting using anti-Hsp65 MoAb and anti-hIL-2 MoAb, respectively. Hsp65-IL-2 and Hsp65 were then purified by Ni-NTA affinity chromatography. Mice were immunized with purified Hsp65-hIL-2 or Hsp65 emulsified in the adjuvant combination dimethyl dioctadecylammonium bromide and mo...

Genetically Engineered Lactococcus lactis Secreting Murine IL-10 Modulates the Functions of Bone Marrow-Derived Dendritic Cells in the Presence of LPS.

Scandinavian Journal of Immunology — Wed, 28 Jan 2009 03:56:44 +0100

Authors: Loos M, Remaut E, Rottiers P, De Creus A Oral delivery of IL-10 by genetically modified Lactococcus lactis (LL-pTmIL10) has been shown to efficiently reduce intestinal inflammation in mice with chronic colitis, but the mechanisms involved have not been elucidated. It has been suggested that IL-10 controls intestinal inflammation by inhibiting microbe-induced activation of dendritic cells. We therefore investigated whether LL-pTmIL10 can modulate the functions of bone marrow-derived dendritic cells (BM-DC) responding to LPS. Incubation of these cells with LL-pTmIL10 or with the control strain LL-pTREX reduced their ability to activate allogeneic T-cell proliferation. However, in contrast to LL-pTREX, LL-pTmIL10 inhibited the LPS-stimulated secretion of MCP-1 by BM-DC and reduce...

Inhibition of Human Neutrophil Apoptosis by Paracoccidioides brasiliensis: Role of Interleukin-8.

Scandinavian Journal of Immunology — Wed, 28 Jan 2009 03:56:33 +0100

Authors: Acorci MJ, Dias-Melicio LA, Golim MA, Bordon-Graciani AP, Peraçoli MT, Soares AM Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidiodes brasiliensis that presents a wide spectrum of clinical manifestations. Because of the great number of neutrophils polymorphonuclear neutrophils (PMN) found in the P. brasiliensis granuloma, studies have been done to evaluate the role of these cells during the development of the infection. This fungus is found intracellularly in PMN and monocytes/macrophages, suggesting that it is capable of evading damage and surviving inside these cells. Thus, in the present study, we investigated whether P. brasiliensis can prolong the lifetime of PMN, and if this process would be related with IL-8 levels. PMN apoptosis and intrace...

Modifying antibody specificity by chain shuffling of V / V between antibodies with related specificities.

Scandinavian Journal of Immunology — Thu, 01 Jan 2009 05:00:00 +0100

Authors: Christensen PA, Danielczyk A, Ravn P, Larsen M, Stahn R, Karsten U, Goletz S Histo-blood group antigens are important markers of developmental stages and as such also often of tumours. Generation of antibodies towards these carbohydrate structures is still a challenging task as they may lack specificity, affinity or are only of the IgM class. We have examined four own antibodies to Lewis Y/H type 2 for their fine specificities using a large panel of mono- and oligosaccharides. Sequence alignment to other antibodies with similar specificity revealed an overall limited variation, and that our antibodies constitute a novel set. Based on produced and analysed chimeric mouse-human antibodies, extensive chain shuffling experiments were performed in order to analyse influences of the...

Inhibition of TNF-alpha-induced cyclooxygenase-2 expression by Mycobacterium bovis BCG in human alveolar epithelial A549 cells.

Scandinavian Journal of Immunology — Thu, 01 Jan 2009 05:00:00 +0100

Authors: Bansal K, Narayana Y, Balaji KN Cyclooxygenase-2 (COX-2) is implicated in pathophysiological processes associated with the initiation or maintenance of host inflammatory responses to infection. Our results demonstrates that Mycobacterium bovis BCG (M. bovis BCG) downregulates tumour necrosis factor-alpha (TNF-alpha)-induced COX-2 gene expression in alveolar epithelial cells by inhibiting the phosphorylations of Raf-1 and p38 kinases. Further, M. bovis BCG-mediated inhibition of COX-2 or p38 mitogen-activated protein kinase could be reversed by Calyculin A, a selective inhibitor of Ser/Thr phosphatases. Moreover, M. bovis BCG inhibited the TNF-alpha-triggered NF-kappaB activation following IkappaB degradation. Taken together, these results suggest that the attenuation of COX-2 ...