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hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sustained extracellular signal-regulated kinase (ERK)-signaling plays a critical role in T-cell-mediated IL-2 production. Although many downstream targets are known for ERK, details remain unknown about which molecules play functional roles in IL-2 production. Here, we addressed this question using proteomic analysis of nuclear proteins from TCR-activated T cells and identified hnRNP-K as one of the ERK targets essential for IL-2 production. hnRNP-K was previously shown by others to be a direct substrate of ERK and form complexes with multiple signaling proteins as well as DNA and RNA. Our data showed a clear ERK-dependent...
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Chang, J.-W., Koike, T., Iwashima, M. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Induction of TNF-alpha-converting enzyme-ectodomain shedding by pathogenic autoantibodiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The release of the soluble form of tumor necrosis factor (TNF)-alpha from the plasma membrane occurs through the activation of the secretase tumor necrosis factor-alpha-converting enzyme (TACE). The current study was designed to examine whether the anti-Ro/SSA autoantibodies (Abs) are capable to regulate TACE expression in non-neoplastic human salivary gland epithelial cells (SGEC) cultures. We investigated the effect of anti-Ro/SSA Abs on the localization and abundance of cell-surface TACE and on TACE pro-domain-shedding and activation. In addition, the potential physiological consequences of TNF-alpha blockage by the bio...
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Sisto, M., Lisi, S., Lofrumento, D. D., Frassanito, M. A., Cucci, L., D'Amore, S., Mitolo, V., D'Amore, M. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Regulatory and pro-inflammatory phenotypes of myelin basic protein-autoreactive T cells in multiple sclerosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MBP-specific autoreactive T cells are considered pro-inflammatory T cells and thought to play an important role in the pathogenesis of multiple sclerosis (MS). Here, we report that MBP83–99-specific T cells generated from MS patients (n = 7) were comprised of pro-inflammatory and regulatory subsets of distinct phenotypes. The pro-inflammatory phenotype was characterized by high production of IFN-, IL-6, IL-21 and IL-17 and low expression of FOXP3, whereas the regulatory subset expressed high levels of FOXP3 and exhibited potent regulatory functions. The regulatory subset of MBP-specific T cells appeared to expand fro...
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Hong, J., Li, H., Chen, M., Zang, Y. C. Q., Skinner, S. M., Killian, J. M., Zhang, J. Z. Tags: Featured article of the month Source Type: journals

Expression of fully assembled TCR-CD3 complex on double positive thymocytes: synergistic role for the PRS and ER retention motifs in the intra-cytoplasmic tail of CD3{varepsilon}Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TCR expression on double-positive (DP) thymocytes is a prerequisite for thymic selection that results in the generation of mature CD4+ and CD8+ single-positive T cells. TCR is expressed at very low level on preselection DP thymocytes and is dramatically up-regulated on positively selected thymocytes. However, mechanism governing TCR expression on developing thymocytes is not understood. In the present report, we demonstrate that the intra-cytoplasmic (IC) domain of CD3 plays a critical role in regulating TCR expression on DP thymocytes. We provide genetic and biochemical evidence to show that the CD3 IC domain mutations re...
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Brodeur, J.-F., Li, S., Damlaj, O., Dave, V. P. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

The study of allergy by Japanese researchers: a historical perspectiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article is aimed at introducing such individual work and how these areas have contributed to our understanding of the mechanisms of allergic reactions. (Source: International Immunology)
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Takai, T., Karasuyama, H. Tags: REVIEWS Source Type: journals

IL-5- and eosinophil-mediated inflammation: from discovery to therapyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IL-5 was originally defined as a T-cell-derived cytokine that triggers activated B cells for terminal differentiation into antibody-secreting plasma cells, at least in mice. Concurrently, IL-5 was recognized as the major maturation and differentiation factor for eosinophils in mice and humans. Over-expression of IL-5 significantly increases eosinophil numbers and antibody levels in vivo. Conversely, mice lacking a functional gene for IL-5 or the IL-5 receptor alpha chain (IL-5R) display a number of developmental and functional impairments in B-cell and eosinophil lineages. In addition to the Janus kinase–signal trans...
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Authors: Kouro, T., Takatsu, K. Tags: REVIEWS Source Type: journals

In this issueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: International Immunology)
Source: International Immunology - November 18, 2009 Category: Allergy & Immunology Tags: IN THIS ISSUE Source Type: journals

Anti-vascular endothelial growth factor (VEGF) specific activity of intravenous immunoglobulin (IVIg)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: International Immunology)
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Damianovich, M., Blank, M., Raiter, A., Hardy, B., Shoenfeld, Y. Tags: CORRIGENDUM Source Type: journals

Critical role of IFN-{gamma} in CFA-mediated protection of NOD mice from diabetes developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IFN- signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN- signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN- receptor-deficient (IFN-R–/–) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN- is necessary for the CFA-med...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Mori, Y., Kodaka, T., Kato, T., Kanagawa, E. M., Kanagawa, O. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Naive CD4 T cells from aged mice show enhanced death upon primary activationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that naive CD4 T cells from aged mice (ANCD4 cells) showed greater apoptosis upon primary activation than those from young (Yg) mice, with loss of mitochondrial membrane potential, poor activation of Rel family transcription factors and increased DNA damage. Their ability to enhance glycolysis, produce lactate and induce autophagy following activation was also compromised. ANCD4 cells remained susceptible to death beyond first cell division. Activated ANCD4 cells also showed poor transition to a ‘central memory’ (CM) CD44high, CD62Lhigh phenotype in vitro. This correlated with low proportions of CM ce...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Mattoo, H., Faulkner, M., Kandpal, U., Das, R., Lewis, V., George, A., Rath, S., Durdik, J. M., Bal, V. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Mitochondrial translocation of the glucocorticoid receptor in double-positive thymocytes correlates with their sensitivity to glucocorticoid-induced apoptosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glucocorticoid receptor (GR) signaling plays an important role in the selection and apoptosis of thymocytes. Besides nuclear translocation, mitochondrial translocation of the ligand-bound GR in lymphoid cells was also shown, which might determine glucocorticoid (GC)-induced apoptosis sensitivity. In the present work, we followed the ligand-induced GR trafficking in CD4+CD8+ double-positive (DP) thymocytes. Using confocal microscopy, we found that upon short-term in vitro GC analog [dexamethasone (DX)] treatment, the GR translocates into the mitochondria but not into the nucleus in DP cells. We also analyzed the GR redistri...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Talaber, G., Boldizsar, F., Bartis, D., Palinkas, L., Szabo, M., Berta, G., Setalo, G., Nemeth, P., Berki, T. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Histidine decarboxylase but not histamine receptor 1 or 2 deficiency protects from K/BxN serum-induced arthritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Serum transfer from arthritic K/BxN mice into naive animals results in arthritis. Mast cells have been shown to be essential since mice lacking these cell type do not develop arthritis upon serum injection. Mast cell function depends on the release of granules filled with mediators such as histamine. Mice deficient in histidine decarboxylase (HDC–/–) that do not produce histamine and mice deficient for histamine receptor 1 (H1R–/–) or histamine receptor 2 (H2R–/–) were injected with arthritogenic sera from the K/BxN mice, and the progression of arthritis was observed through the next 2 w...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Rajasekaran, N., Solomon, S., Watanabe, T., Ohtsu, H., Gajda, M., Brauer, R., Illges, H. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Apoptosis of lymphocytes and monocytes infected with influenza virus might be the mechanism of combating virus and causing secondary infection by influenzaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Influenza affects most of the world's population annually, often causing a secondary infection, but pathological mechanisms of influenza virus infection remain unclear. We have found that influenza viruses have a selective preference for infecting monocytes and mature immune effector cells. This paper provides evidence that influenza virus infection increases the expression of granzyme B (GrB) in monocytes, activated T and B cells. All GrB+ cells had cytolytic function. GrB+CD62Lhigh central memory (TCM) cells were fast response population to virus infection when compared with GrB+CD62Llow population. The influenza virus-i...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Xie, D., Bai, H., Liu, L., Xie, X., Ayello, J., Ma, X., Zhang, J. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Recombinant YopJ induces apoptosis in murine peritoneal macrophages in vitro: involvement of mitochondrial death pathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Yersinia species during infection adhere to host immune cells primarily to macrophages and employ its secretary proteins known as Yersinia outer proteins to trigger death in infected cells. In the present study, it is shown that recombinant Yersinia outer protein J (rYopJ) could induce apoptosis in murine peritoneal macrophages in vitro as assessed by morphological features, internucleosomal DNA fragmentation, change in mitochondrial membrane potential (MMP) (m), activation of caspases and Annexin V binding. rYopJ-induced cell death was dose and time dependent. Pre-treatment with broad-spectrum caspase inhibitor Z-VAD-FMK,...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Pandey, A. K., Sodhi, A. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Enhanced B cell activation in the absence of CD81Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD81 is a component of the CD19/CD21 co-receptor complex in B cells. However, the role of CD81 in B cell activation has not been clearly elucidated. Here, we demonstrate that Cd81–/– B cells stimulated via their B cell receptor fluxed higher intracellular-free calcium ion along with increased phosphorylation of spleen tyrosine kinase and phospholipase gamma 2. Additionally, Cd81–/– B cells responded to toll like receptor 4 stimulation with increased nuclear factor-kappa B activation, cell proliferation and antibody secretion compared with wild-type B cells. Cd81–/– mice also mounted a si...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Sanyal, M., Fernandez, R., Levy, S. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

CD4 T cell cooperation is required for the in vivo activation of CD4 T cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We address here the role of CD4 T cell cooperation in the activation of CD4 T cells. Administration of aggregated hen egg lysozyme (HEL) without microbial adjuvant to BALB/c mice normally generates cytokine-producing CD4 T cells specific for the HEL major peptide, HEL105–120, as well as CD4 T cells specific for HEL non-major peptides. The prior administration of HEL105–120 ablates the generation of cytokine-secreting CD4 T cells specific for HEL105–120, as well as the CD4 T cells specific for HEL non-major peptides, normally generated upon HEL challenge. Thus, the activation of HEL non-major peptide-speci...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Peters, N. C., Kroeger, D. R., Mickelwright, S., Bretscher, P. A. Tags: Featured article of the month Source Type: journals

Morbus Crohn--a disease of failing macroautophagy in the immune system?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in genes involved in macroautophagy have been found to be associated with Morbus Crohn, also called Crohn's disease (CD), an inflammatory bowel disease. Taking this disease as an example for pathogenesis due to altered macroautophagy, we discuss here how macroautophagy supports innate and adaptive immunity. This support ranges from maintenance of components of the immune system, antigen processing for presentation to the immune system, to education of the immune system in order to distinguish self from dangerous non-self. A better understanding of these mechanisms should allow us not only to develop therapeutical...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Meixlsperger, S., Munz, C. Tags: Review article Source Type: journals

Molecular basis of canonical and bactericidal autophagyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is a catabolic process by which cells degrade their own cytoplasmic constituents. Cells respond to the stress response of nutrient deficiency by degrading a portion of their cellular components to produce amino acids and energy. Recently, it became evident that the autophagic machinery is also involved in a kind of innate immune system. Some bacteria that invade mammalian cells are eventually entrapped in an autophagic membrane structure. In this review, we describe the current understanding of three of the basic components of the canonical autophagy machinery—LC3, the Atg16L complex and phosphatidylinosito...
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Noda, T., Yoshimori, T. Tags: Review article Source Type: journals

In this issueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: International Immunology)
Source: International Immunology - October 26, 2009 Category: Allergy & Immunology Tags: IN THIS ISSUE Source Type: journals

Lactoferrin modulation of BCG-infected dendritic cell functionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the potential of lactoferrin to modulate surface expression of MHC II, CD80, CD86 and CD40 from bone marrow-derived dendritic cells (BMDCs) was examined. Generally, lactoferrin decreased pro-inflammatory cytokines [tumor necrosis factor (TNF)-, IL-6 and IL-12p40] and chemokines [macrophage inflammatory protein (MIP)-1 and MIP-2] and increased regulatory cytokine, transforming growth factor-β1 and a T-cell chemotatic factor, monocyte chemotactic protein-1, from uninfected or BCG-infected BMDCs. Culturing BCG-infected BMDCs with lactoferrin also enhanced their ability to respond to IFN- activation through...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Hwang, S.-A., Actor, J. K. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease. (Source: International Immunology)
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Gil, L., Lopez, C., Lazo, L., Valdes, I., Marcos, E., Alonso, R., Gambe, A., Martin, J., Romero, Y., Guzman, M. G., Guillen, G., Hermida, L. Tags: Featured article of the month Source Type: journals

Amyloid precursor family proteins are expressed by thymic and lymph node stromal cells but are not required for lymphocyte developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pharmacological inhibitors that block amyloid precursor protein (APP) cleavage and the formation of senile plaques are under development for the treatment of familial Alzheimer's disease. Unfortunately, many inhibitors that block -secretase-mediated cleavage of APP also have immunosuppressive side effects. In addition to APP, numerous other proteins undergo -secretase-mediated cleavage. In order to develop safer inhibitors, it is necessary to determine which of the -secretase substrates contribute to the immunosuppressive effects. Because APP family members are widely expressed and are reported to influence calcium flux, t...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Laky, K., Annaert, W., Fowlkes, B. J. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responsesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Activated mature T cells induce various inhibitory receptors implicated in maintaining peripheral tolerance in response to the trans-acting ligands. Interestingly, paired Ig-like receptor (PIR)-B, an inhibitory MHC class I receptor on B cells and myeloid cells, could be involved in regulating early T cell development because epitope for PIR is detected on pre-thymic T/NK progenitors but not on thymocytes or mature T cells. We hypothesized that PIR-B is not only a regulator for T cell development but is also detrimental if expressed on mature T cells. Here we demonstrated, using PIR-B-deficient fetuses, that PIR-B is indeed...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Imada, M., Masuda, K., Satoh, R., Ito, Y., Goto, Y., Matsuoka, T., Endo, S., Nakamura, A., Kawamoto, H., Takai, T. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Time-lapse observation of cellular function with fluorescent probe reveals novel CTL-target cell interactionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fluorescent protein that detects caspase-3 activation was used for the time-lapse observation of CTL–target cell interaction. In the target cells transfected with SCAT3.1 (caspase-3-sensitive fusion protein) complementary DNA, caspase-3 activation can be detected significantly earlier than the commonly used annexin-V binding that detects membrane change in apoptotic cells. Moreover, during the cytolytic interaction between OE4 CTL and W3 tumor target cells, detachment of CTL from the target cells occurred prior to caspase-3 activation and death of the target cells, indicating very early sensing of apoptotic target ce...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Tomura, M., Mori, Y. S., Watanabe, R., Tanaka, M., Miyawaki, A., Kanagawa, O. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

A novel approach to induce human DCs from monocytes by triggering 4-1BBL reverse signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte-derived DCs (Mo-DCs) from human monocytes using anti-4-1BB ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven Mo-DCs (DCs-4-1BBL) not only express higher levels of CD86, CD83 and HLA-DR, when compared with the Mo-DCs matured by tumor necrosis factor , but also exhibit a unique phenotype that expresses lower levels of PD-L1. High levels of GM-CSF, M-CSF and Flt3 ligand (FL) were found in the anti-4-1BBL-differentiation culture. Neutra...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Ju, S., Ju, S., Ge, Y., Qiu, H., Lu, B., Qiu, Y., Fu, J., Liu, G., Wang, Q., Hu, Y., Shu, Y., Zhang, X. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Protective role of mouse MBL-C on intestinal mucosa during Shigella flexneri invasionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mannan-binding lectin (MBL) is a C-type serum lectin, which is believed to play an important role in the innate immunity against a variety of pathogens. MBL can bind to sugar determinants of a wide variety of microorganisms, neutralize them and inhibit infection by complement activation through the lectin pathway and opsonization by collectin receptors. Given that small intestine is a predominant site of extrahepatic expression of MBL, here we addressed the question whether MBL is involved in mucosal innate immunity. The carbohydrate recognition domain (CRD) genes of mouse MBL-C (mMBL-C) were cloned and expressed in Escher...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Zuo, D.-M., Zhang, L.-Y., Lu, X., Liu, Y., Chen, Z.-L. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Nitric oxide cooperates with glucocorticoids in thymic epithelial cell-mediated apoptosis of double positive thymocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
T cell development in the thymus is controlled by thymic epithelial cells (TE). While it is accepted that TE interact with maturing T cells, the mechanisms by which they trigger ‘death by neglect’ of double-positive (DP) thymocytes are poorly understood. We and others have demonstrated a role for TE-derived glucocorticoids (GCs) in this process. We have studied TE-induced apoptosis using an in vitro system based on co-culturing a thymic epithelial cell line (TEC) with DP thymic lymphoma cells or thymocytes (DP thymic cells). Here, we demonstrate that nitric oxide (NO·) is also involved in this death proc...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Cohen, O., Kfir-Erenfeld, S., Spokoini, R., Zilberman, Y., Yefenof, E., Sionov, R. V. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Regulatory T cells: how do they suppress immune responses?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. One of the key issues for understanding Treg function is to determine how they suppress other lymphocytes at the molecular level in vivo and in vitro. Here we propose that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3)+ Treg in vivo and in vitro in mice and humans. When this central mechanism is abrogated, it causes a breach in self-tolerance and immune homeostasis. Other suppressive mechanisms may synergistically operate with this common mechanism depending...
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Sakaguchi, S., Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T. Tags: REVIEWS Source Type: journals

The study of regulatory T cells and NKT cells in Japan: a historical perspectiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immune regulation plays an important role in maintaining homeostasis of the immune system. A number of Japanese immunologists have made significant contributions to the elucidation of the mechanisms of immune regulation. In particular, lymphocyte populations that could regulate immune responses—for example regulatory T cells and NKT cells—have been extensively analyzed. Here, we present an overview of research on immune regulation by highlighting the work of several Japanese contributors. (Source: International Immunology)
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Arase, H., Seino, K.-i. Tags: REVIEWS Source Type: journals

In this issueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: International Immunology)
Source: International Immunology - September 23, 2009 Category: Allergy & Immunology Tags: IN THIS ISSUE Source Type: journals

Induction of IL-10- and IFN-{gamma}-producing T-cell responses by autoreactive T-cells expressing human T-cell leukemia virus type I TaxEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia, HTLV-I-associated myelopathy/tropical spastic paraparesis and various autoimmune-like disorders. T-cell immune suppression is also associated with HTLV-I infection. Mechanisms of diverse immune dysregulation in HTLV-I infection are obscure. Here, we investigated a potential link between autoimmunity and immune suppression in HTLV-I infection. G14, an IL-2-dependent HTLV-I-negative CD4+CD8+ T-cell line previously established from an HTLV-I-infected rat, constantly proliferated and produced IFN-. IFN- production by G14 cells was dependent o...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Takatsuka, N., Hasegawa, A., Takamori, A., Shimizu, Y., Kato, H., Ohashi, T., Amagasa, T., Masuda, T., Kannagi, M. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Activation of the mouse TCR{gamma} enhancers by STAT5Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The IL-7R controls local accessibility of joining (J) gene segments in the mouse TCR locus by recruiting signal transducers and activators of transcription (STAT) 5 and transcriptional coactivators to the J germ line promoters and inducing histone acetylation and germ line transcription. Because STAT consensus motifs are conserved not only in the J promoters but also in the TCR 3' enhancer (E) elements, it is possible that STAT5 interacts with and activates E. To address this question, we first showed that the lysine 4 residue of histone H3 is substantially methylated at E1 and E4 elements in wild-type early thymocytes and...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Tani-ichi, S., Satake, M., Ikuta, K. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+CD25Hi regulatory T cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Regulatory CD4+CD25Hi T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. However, the underlying mechanisms by which they impact antigen-specific CD8+ immune responses in cancer patients and how they interact with each other under physiologic conditions remain unclear. Herein, we examined the relationship of PD-1 and its abrogation to the function of Treg in patients with melanoma using short-term in vitro assays to generate melanoma-specific T cells. We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Wang, W., Lau, R., Yu, D., Zhu, W., Korman, A., Weber, J. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Anti-vascular endothelial growth factor (VEGF) specific activity of intravenous immunoglobulin (IVIg)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Intravenous immunoglobulins (IVIg) preparations can be beneficial therapeutic agents for the treatment of tumor metastases as has been shown in both human and animal studies. Operating mechanisms have not yet been completely elucidated. Some of the mechanisms proposed entail the stimulation of the production of IL-12, a cytokine that exhibits anti-angiogenic activities, as well as inhibition of endothelial cells proliferation and vascular endothelial growth factor (VEGF) secretion. The aim of the present study was to investigate whether in an IVIg preparation there are natural antibodies directed against VEGF with the pote...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Damianovich, M., Blank, M., Raiter, A., Hardy, B., Shoenfeld, Y. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Differential preferences in serosal homing and distribution of peritoneal B-cell subsets revealed by in situ CFSE labelingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Peritoneal B cells represent a heterogeneous mixture of mature peripheral B lineage subsets with distinct developmental and functional characteristics. Here, we report that a single intraperitoneal injection of intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester (CFSE) results in the stable fluorescent labeling of resident lymphocytes, without dissipation of the tracer compound into other peripheral lymphoid organs. Using this in situ labeling procedure followed by multicolor flow cytometry or tissue fluorescence at various periods for up to 4 weeks post-labeling, we demonstrate that the distinct ...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Labadi, A., Balogh, P. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

A functional soluble form of CTLA-4 is present in the serum of celiac patients and correlates with mucosal injuryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Celiac disease (CD) is a multifactorial disorder influenced by environmental, genetic and immunological factors. Increasing evidence showed CTLA-4 gene as an important susceptibility locus for autoimmune disorders. A native soluble cytotoxic T-lymphocyte-associated protein-4 (sCTLA-4), lacking of transmembrane sequence, has been described in several autoimmune diseases. We aimed to evaluate the presence of increased sCTLA-4 concentration in the serum of patients with CD and the possible immunoregulatory function. Blood samples were collected from 160 CD patients; sCTLA-4 levels were evaluated by ELISA, western blot and rev...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Simone, R., Brizzolara, R., Chiappori, A., Milintenda-Floriani, F., Natale, C., Greco, L., Schiavo, M., Bagnasco, M., Pesce, G., Saverino, D. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Modulation of the TCR stimulation strength can render human activated CD4+ T cells suppressiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we explored the potential of human naive CD4+ T cells to acquire regulatory properties upon stimulation. We demonstrated that, in vitro, pre-activated naive CD4+CD25–CD45RA+ T cells could become anergic and suppressive CD4+CD25+ T cells upon lower intensity TCR stimulation. These CD4+CD25+ T cells generated in vitro potently suppress the proliferation of allogenic CD4+CD25– T cells independently of cytokines and in a contact-dependent manner. Our data indicate that expression of Foxp3 is not necessary to induce the suppressive T cell activity. We demonstrate that these CD4+CD25+ T cells are unres...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Noel, G., Brinster, C., Semana, G., Bruniquel, D. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

A novel immunoregulatory protein in human colostrum, syntenin-1, for promoting the development of IgA-producing cells from cord blood B cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human colostrum contains many bioactive factors that must promote the development of intestinal mucosal immunity in infants. Especially, the presence of certain cytokines such as transforming growth factor (TGF)-β or IL-10 has been of great interest for IgA production as a function of mucosal immune response. In the present study, we attempted to investigate whether unidentified factors inducing generation of IgA-producing cells from naive B cells might exist in colostrum. For this purpose, colostrum samples were directly added to a culture consisting of naive B cells and dendritic cells from cord blood and CD40 ligan...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Sira, M. M., Yoshida, T., Takeuchi, M., Kashiwayama, Y., Futatani, T., Kanegane, H., Sasahara, A., Ito, Y., Mizuguchi, M., Imanaka, T., Miyawaki, T. Tags: Featured article of the month Source Type: journals

Primary immune deficiencies affecting lymphocyte differentiation: lessons from the spectrum of resulting infectionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Understanding primary immunodeficiencies has elucidated many aspects of human immunity and susceptibility to infections. Recently, defects have been identified that result in deficiencies of terminally differentiated subsets of lymphocytes including deficiencies of memory B cells, NKT cells and Th17 T cells. Together with defects specific to Th1 responses, these disorders revealed that dedicated pathogen-specific mechanisms exist for prevalent human pathogens, and that some host defence strategies are remarkably specific. Deficiency of Th17 cells confirms that this subset of effector T cells is important for defence at epi...
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Cook, M. C., Tangye, S. G. Tags: REVIEW Source Type: journals

In this issueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: International Immunology)
Source: International Immunology - August 24, 2009 Category: Allergy & Immunology Tags: IN THIS ISSUE Source Type: journals

CCR1 expression and signal transduction by murine BMMC results in secretion of TNF-{alpha}, TGF{beta}-1 and IL-6Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we report for the first time that murine bone marrow-derived mast cells (BMMC) express messenger RNA and protein for CCR1. BMMC cultured in the presence of murine recombinant stem cell factor and murine IL-3 expressed CCR1 after 5–6 weeks. We also report for the first time that mBMMCCCR1+ cells endogenously express neurokinin receptor-1 and intercellular adhesion molecule-1. To examine the activity of CCR1 on these BMMC, we simultaneously stimulated two receptors: CCR1 by its ligand macrophage inflammatory protein-1 and the IgE receptor FcRI by antigen cross-linking. We found that co-stimulation enhanc...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Fifadara, N. H., Aye, C. C., Raghuwanshi, S. K., Richardson, R. M., Ono, S. J. Tags: Featured article of the month Source Type: journals

Bacillus subtilis-specific poly-{gamma}-glutamic acid regulates development pathways of naive CD4+ T cells through antigen-presenting cell-dependent and -independent mechanismsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Peripheral naive CD4+ T cells selectively differentiate to type 1 Th, type 2 Th and IL-17-producing Th (Th17) cells, depending on the priming conditions. Since these subsets develop antagonistically to each other to elicit subset-specific adaptive immune responses, balance between these subsets can regulate the susceptibility to diverse immune diseases. The present study was undertaken to determine whether poly--glutamic acid (-PGA), an edible and safe exopolymer that is generated by microorganisms such as Bacillus subtilis, could modulate the development pathways of Th subsets. The presence of -PGA during priming promoted...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Kim, S., Yang, J. Y., Lee, K., Oh, K. H., Gi, M., Kim, J. M., Paik, D. J., Hong, S., Youn, J. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we aimed to identify novel genes involved in experimental and human asthma, importance of which has not yet been recognized. In an ovalbumin-induced murine model of asthma, we applied microarray gene expression analysis at different time points after allergen challenges. Advanced statistical methods were used to relate gene expression changes to cellular processes and to integrate our results into multiple levels of information available in public databases. At 4 h after the first allergen challenge, gene expression pattern reflected mainly an acute, but non-atopic, inflammatory response and strong chemotact...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Tolgyesi, G., Molnar, V., Semsei, A. F., Kiszel, P., Ungvari, I., Pocza, P., Wiener, Z., Komlosi, Z. I., Kunos, L., Galffy, G., Losonczy, G., Seres, I., Falus, A., Szalai, C. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Light chain-deficient mice produce novel multimeric heavy-chain-only IgA by faulty class switchingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recently, we identified that diverse heavy chain (H-chain)-only IgG is spontaneously produced in light chain (L-chain)-deficient mice (L–/– with silenced and loci) despite a block in B cell development. In murine H-chain IgG, the first C exon, CH1, is removed after DNA rearrangement and secreted polypeptides are comparable with camelid-type H-chain IgG. Here we show that L–/– mice generate a novel class of H-chain Ig with covalently linked chains, not identified in any other healthy mammal. Surprisingly, diverse H-chain-only IgA can be released from B cells at levels similar to conventional IgA and ...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Matheson, L. S., Osborn, M. J., Smith, J. A., Corcos, D., Hamon, M., Chaouaf, R., Coadwell, J., Morgan, G., Oxley, D., Bruggemann, M. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed mechanisms of the DNA strand cleavage in SHM and CSR are still largely unknown. Recently, the apurinic/apyrimidinic endonucleases, Apex1 and Apex2, were reported to be involved in the DNA cleavage step of CSR. Here, we examined the role of Apex2 in SHM using Apex2-deficient mice and found that the Apex2 deficiency caused a drastic reduction in the frequency of SHM and the number of mutations per mutated clone without affecting the p...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Sabouri, Z., Okazaki, I.-m., Shinkura, R., Begum, N., Nagaoka, H., Tsuchimoto, D., Nakabeppu, Y., Honjo, T. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Nucleotide-hydrolyzing antibodies from the sera of autoimmune-prone MRL-lpr/lpr miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abzymes (Abzs) with different enzymic activities have been detected in the sera of patients with various autoimmune (AI) diseases and in AI mice. In this work, electrophoretically homogeneous IgGs were isolated from the sera of MRL-lpr/lpr mice spontaneously developing lupus-like AI pathology. It was shown for the first time that polyclonal IgGs (pIgGs) and their isolated heavy and light chains hydrolyze different nucleoside-5'-triphosphate (NTPs), nucleoside-5'-diphosphate (NDPs), adenosine monophosphate and deoxiadenosine-5'-monophosphate (dAMP), whereas antibodies from the sera of control healthy mice were catalytically...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Andryushkova, A. A., Kuznetsova, I. A., Orlovskaya, I. A., Buneva, V. N., Nevinsky, G. A. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Mutational analysis of Cys88 of Toll-like receptor 4 highlights the critical role of MD-2 in cell surface receptor expressionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides evidence that MD-2 possesses potential ability to play an essential role in cell surface expression of TLR4. (Source: International Immunology)
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Nishitani, C., Takahashi, M., Mitsuzawa, H., Shimizu, T., Ariki, S., Matsushima, N., Kuroki, Y. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-{alpha} through an ERK1/2-dependent pathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Antibodies specific to moesin, which are frequently detectable in the serum of patients with aplastic anemia (AA), can induce tumor necrosis factor- (TNF-) secretion from monocytes and a human monocytic leukemia cell line THP-1. We investigated the mechanisms responsible for TNF- secretion from monocytic cells induced by the auto-antibodies that are purified from the sera of AA patients. TNF- induction by anti-moesin antibodies depended on the amount of cell surface moesin expressed by THP-1 cells. F(ab')2 fragments prepared from the anti-moesin antibodies were able to stimulate THP-1 cells to secrete TNF- and this stimula...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Espinoza, J. L., Takamatsu, H., Lu, X., Qi, Z., Nakao, S. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

Antimicrobial cathelicidin polypeptide CAP11 suppresses the production and release of septic mediators in D-galactosamine-sensitized endotoxin shock miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, to clarify the protective mechanism of CAP11 against endotoxin shock, we evaluated the effects of CAP11 on the production and release of septic mediators in vitro and in vivo using a murine macrophage cell line RAW264.7 and a D-galactosamine-sensitized murine endotoxin shock model. LPS stimulation induced the production of inflammatory cytokines and anandamide and release of HMGB1 from RAW264.7 cells. Importantly, CAP11 suppressed the LPS-induced production and release of these mediators by RAW264.7 cells. Moreover, LPS administration enhanced the serum levels of HMGB1, anandamide and inflammatory cytokines ...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Murakami, T., Obata, T., Kuwahara-Arai, K., Tamura, H., Hiramatsu, K., Nagaoka, I. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals

The CD70-CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD70 expressed on dendritic cells (DCs) has been shown to play a critical role in inducing effective CD8+ T cell responses and a Th1 response in mice. However, it has not been extensively examined whether human primary DCs express CD70 and whether the CD70–CD27 interaction promotes naive CD4+ T cells to acquire the ability to produce effector cytokines during the DC–T cell interaction in humans. Here, we show that human myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells stimulated with CD40 ligand together with pro-inflammatory cytokines or Toll-like receptor ligands express CD70. Thymic stromal ly...
Source: International Immunology - July 26, 2009 Category: Allergy & Immunology Authors: Hashimoto-Okada, M., Kitawaki, T., Kadowaki, N., Iwata, S., Morimoto, C., Hori, T., Uchiyama, T. Tags: ORIGINAL RESEARCH PAPERS Source Type: journals