Molecular analysis of TCR junctional variability in individual infiltrated islets of non-obese diabetic mice: evidence for the constitution of largely autonomous T cell foci within the same pancreas.

Abstract:

:Insulitis develops in non-obese diabetic (NOD) mice as a multicentric and asynchronous process. In an effort to understand how this T cell mediated process expands within each islet and propagates between the islets of the same pancreas, we have analyzed the junctional diversity of TCR V beta 6 and V beta 8.2 transcripts cloned from infiltrated islets. The material examined was obtained from individual islets of 8 and 12 week old NOD mice or from pooled islets of 4 week old individual mice. Compared with spleen transcripts, where every V beta 6 or V beta 8.2 clone displays a different junction, islet transcripts are considerably less diverse. Each islet harbors from one to a maximum of six independent CDR3 sequences out of 10 or more analyzed colonies. On the other hand, there is an overall diversity of sequences when comparing the islets of the same pancreas or individual mice at 4 weeks. Altogether, these results support the idea that TCR repertoires are already divergent at the very early onset of insulitis and that each islet-centered infiltrate develops rather autonomously from the oligoclonal expansion of a limited set of precursors. Recirculation between islets is limited and does not seem to be the main mode of propagation of insulitis. Finally, a close analysis of J beta usage and N additions in beta chain transcripts from infiltrating cells reveals definite biases suggestive of an ongoing selective process imposed upon intra-pancreatic T lymphocytes.

journal_name

Int Immunol

journal_title

International immunology

authors

Sarukhan A,Bedossa P,Garchon HJ,Bach JF,Carnaud C

doi

10.1093/intimm/7.1.139

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

139-46

issue

1

eissn

0953-8178

issn

1460-2377

journal_volume

7

pub_type

杂志文章
  • Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage.

    abstract::We investigated the role of IL-7 receptor alpha (IL-7Ralpha) signal in the formation of Peyer's patch (PP) anlage. Although pan-lymphopenia is a common phenotype of rag2-/- and il7ralpha-/- mice, a close inspection revealed nodules corresponding to PP in the adult rag2-/- but not in the il7ralpha-/- mouse. In our prev...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.1.1

    authors: Adachi S,Yoshida H,Honda K,Maki K,Saijo K,Ikuta K,Saito T,Nishikawa SI

    更新日期:1998-01-01 00:00:00

  • STAT6, NF-kappaB and C/EBP in CD23 expression and IgE production.

    abstract::STAT6, NF-kappaB (p50) and C/EBPbeta transcription factors (TF) were examined with respect to CD23 regulation. Electrophoretic mobility shift assay (EMSA), competition and supershift analysis demonstrated that STAT6 binds the CD23a promoter but with a lower affinity than the consensus site. STAT6-/- mice were analyzed...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.10.1529

    authors: Tinnell SB,Jacobs-Helber SM,Sterneck E,Sawyer ST,Conrad DH

    更新日期:1998-10-01 00:00:00

  • Localization of intestinal intraepithelial T lymphocytes involves regulation of alphaEbeta7 expression by transforming growth factor-beta.

    abstract::Induction of alphaEbeta7 expression on T cells by transforming growth factor (TGF)-beta is thought to be important for intestinal intraepithelial T lymphocyte (IEL) entry into the epithelial compartment. However, there has been no in vivo evidence that up-regulation of alphaEbeta7 expression on T cells by TGF-beta is ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/14.4.339

    authors: Suzuki R,Nakao A,Kanamaru Y,Okumura K,Ogawa H,Ra C

    更新日期:2002-04-01 00:00:00

  • Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells.

    abstract::BALB/c mice injected at birth with 10(8) semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodies bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/4.1.67

    authors: de la Hera M,de la Hera A,Ramos A,Buelta L,Alonso JL,Rodriguez-Valverde V,Merino J

    更新日期:1992-01-01 00:00:00

  • Molecular genetic features reflecting the preference for isotype switching to IgA expression by Peyer's patch germinal center B cells.

    abstract::It has proven difficult to evaluate the functional potential of germinal center (GC) B cells, including those from Peyer's patches (PP), by either in vivo or in vitro methods. Thus, rather than assess secreted Ig product as an indicator of functional potential we have instead sought to detect mRNAs related to the vari...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/3.12.1253

    authors: Weinstein PD,Schweitzer PA,Cebra-Thomas JA,Cebra JJ

    更新日期:1991-12-01 00:00:00

  • Human skin-derived keratinocytes and fibroblasts co-cultured on 3D poly ε-caprolactone scaffold support in vitro HSC differentiation into T-lineage committed cells.

    abstract::In humans, the thymus is the primary lymphoid organ able to support the development of T cells through its three-dimensional (3D) organization of the thymic stromal cells. Since a remarkable number of similarities are shared between the thymic epithelial cells (TECs) and skin-derived keratinocytes and fibroblasts, in ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxt035

    authors: Palamaro L,Guarino V,Scalia G,Antonini D,De Falco L,Bianchino G,Fusco A,Romano R,Grieco V,Missero C,Del Vecchio L,Ambrosio L,Pignata C

    更新日期:2013-12-01 00:00:00

  • Physiological up-regulation of inhibitory receptors Fc gamma RII and CR1 on memory B cells is lacking in SLE patients.

    abstract::Under physiological conditions immune complexes (IC) are efficiently cleared from the circulation and meanwhile provide important feedback signals for the immune system via Fc gamma Rs and complement receptors. Dysregulation of these mechanisms have been implicated in conditions where IC concentrations reach pathologi...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxm132

    authors: Isaák A,Gergely P Jr,Szekeres Z,Prechl J,Poór G,Erdei A,Gergely J

    更新日期:2008-02-01 00:00:00

  • Cloning of follistatin-related protein as a novel autoantigen in systemic rheumatic diseases.

    abstract::In an attempt to identify autoantigens of synovium in rheumatoid arthritis (RA), we constructed lambda phage expression cDNA libraries from synovium and screened them by IgG purified from synovial fluids, both of which were derived from RA patients. As a result of this unique combination of the libraries and probes, w...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.9.1305

    authors: Tanaka M,Ozaki S,Osakada F,Mori K,Okubo M,Nakao K

    更新日期:1998-09-01 00:00:00

  • Human milk proteins including secretory IgA fail to elicit tolerance after feeding.

    abstract::Oral administration of large doses of protein antigen generally induces a state of systemic unresponsiveness currently termed mucosally induced tolerance. In this study, we used human milk protein (HMP) without casein as a multi-protein antigen for the study of mucosally induced tolerance. The HMP utilized in this stu...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.4.537

    authors: Yuki Y,Fujihashi K,Yamamoto M,McGhee JR,Kiyono H

    更新日期:1998-04-01 00:00:00

  • Maintenance of clonal anergy by endogenously produced IL-10.

    abstract::Inadequate co-stimulation of tumor reactive T cells may contribute to the fact that antigenic tumors are not normally rejected by the immune system. We recently reported that the induction of profound unresponsiveness in a T cell clone by melanoma cells expressing MHC class II antigens may provide a mechanism for thes...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.10.1605

    authors: Becker JC,Czerny C,Bröcker EB

    更新日期:1994-10-01 00:00:00

  • House dust mite allergen Der p 1 elevates the release of inflammatory cytokines and expression of adhesion molecules in co-culture of human eosinophils and bronchial epithelial cells.

    abstract::House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are principal effector cells of allergic inflammation and their adhesion onto human bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule-1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoide...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxl065

    authors: Wong CK,Li ML,Wang CB,Ip WK,Tian YP,Lam CW

    更新日期:2006-08-01 00:00:00

  • Exposure of resting peripheral blood T cells to HIV-1 particles generates CD25+ killer cells in a small subset, leading to induction of apoptosis in bystander cells.

    abstract::Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and CD8+ T cells. We previously showed that resting peripheral blood T cells derived from healthy donors were killed by an apoptotic mechanism after adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles, more effectively than pare...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/9.10.1453

    authors: Kameoka M,Suzuki S,Kimura T,Fujinaga K,Auwanit W,Luftig RB,Ikuta K

    更新日期:1997-10-01 00:00:00

  • Tyk2 is a therapeutic target for psoriasis-like skin inflammation.

    abstract::Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis. In this study, we investigated the role of Tyk2 in IL-23-induced psoriasis-like skin inflammation. Tyk2(-/-) mice when injected with IL-23 showed significant...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxt062

    authors: Ishizaki M,Muromoto R,Akimoto T,Sekine Y,Kon S,Diwan M,Maeda H,Togi S,Shimoda K,Oritani K,Matsuda T

    更新日期:2014-05-01 00:00:00

  • Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells.

    abstract::Human dendritic cells (DC) generated from CD34+ hematopoietic progenitors cultured in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha are related to Langerhans cells (DLC) and have been shown to induce a strong proliferation of allogeneic CD4+ T cells. Th...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.8.1177

    authors: Caux C,Massacrier C,Vanbervliet B,Barthelemy C,Liu YJ,Banchereau J

    更新日期:1994-08-01 00:00:00

  • TCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death.

    abstract::T lymphocytes (pivotal in many inflammatory pathologies) are targets for glucocorticoid hormone (GC). How TCR-mediated activation and GC signaling via glucocorticoid receptor (GR) impact on T-cell fates is not fully defined. We delineated here the expression of a recently identified glucocorticoid-induced TNF receptor...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh134

    authors: Zhan Y,Funda DP,Every AL,Fundova P,Purton JF,Liddicoat DR,Cole TJ,Godfrey DI,Brady JL,Mannering SI,Harrison LC,Lew AM

    更新日期:2004-09-01 00:00:00

  • Endothelial cell co-stimulation through OX40 augments and prolongs T cell cytokine synthesis by stabilization of cytokine mRNA.

    abstract::Human endothelial cells (ECs) constitutively express OX40L and co-stimulate memory CD4(+) T cell proliferation that is dependent upon OX40-OX40L interaction. In vivo, OX40 prolongs T cell survival; however, an unanswered question is whether it can also prolong synthesis of proliferation-sustaining cytokines such as IL...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh255

    authors: Mestas J,Crampton SP,Hori T,Hughes CC

    更新日期:2005-06-01 00:00:00

  • Dendritic cells at a DNA vaccination site express the encoded influenza nucleoprotein and prime MHC class I-restricted cytolytic lymphocytes upon adoptive transfer.

    abstract::Intradermal inoculation of plasmids expressing antigens that contain MHC class I-restricted epitopes leads to the induction of specific CD8(+) cytotoxic T lymphocytes (CTL). The role of in situ transfected antigen-presenting cells (APC) in the priming of specific CTL subsequent to intradermal DNA immunization was inve...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/12.6.825

    authors: Bot A,Stan AC,Inaba K,Steinman R,Bona C

    更新日期:2000-06-01 00:00:00

  • V beta 6-bearing T cells are involved in resistance to Trypanosoma cruzi infection in XID mice.

    abstract::BALB.xid mice, carrying an X-linked mutation leading to the absence of CD5+ B cells, are highly resistant to Trypanosoma cruzi infection. These mice clear blood parasites in the acute phase of infection and do not develop the inflammatory infiltration characteristically observed in the chronic phase of susceptible str...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/8.8.1213

    authors: Cordeiro da Silva A,Lima EC,Vicentelli MH,Minoprio P

    更新日期:1996-08-01 00:00:00

  • A model of suppression of the antigen-specific CD4 T cell response by regulatory CD25+CD4 T cells in vivo.

    abstract::Despite intense recent interest, the suppressive mechanisms of regulatory CD25+CD4 T cells remain poorly understood. One deficiency in the field is the lack of in vivo models where the effects of regulatory CD25+CD4 T cells on antigen-specific responder T cells can be measured quantitatively. We describe one such mode...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh213

    authors: Thorstenson KM,Herzovi L,Khoruts A

    更新日期:2005-04-01 00:00:00

  • Ligand specificities of mouse complement receptor types 1 (CR1) and 2 (CR2) purified from spleen cells.

    abstract::Murine complement receptor type 2 (MCR2) is homologous to human CR2, whereas murine CR1 (MCR1) is structurally and evolutionary different from human CR1. Since ligand specificities of MCR1 and MCR2 are not completely clarified, we analyzed their functional characteristics to correlate them with structural information ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.4.337

    authors: Pramoonjago P,Takeda J,Kim YU,Inoue K,Kinoshita T

    更新日期:1993-04-01 00:00:00

  • Self-restricted primary human histocompatibility leukocyte antigen (HLA)-specific cytotoxic T lymphocytes.

    abstract::The specificity of self MHC-restricted T cells responding to peptide fragments of processed antigen has been well characterized. However, the means by which alloreactive T lymphocytes recognize MHC alloantigen remain poorly understood. We now provide evidence that the recognition of class I human leukocyte antigen (HL...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.1.103

    authors: Breur-Vriesendorp BS,Ivanyi P

    更新日期:1993-01-01 00:00:00

  • Osteoclasts support the survival of human plasma cells in vitro.

    abstract::The aim of this in vitro study was to evaluate if osteoclasts (OCs) and dendritic cells (DCs), both of monocyte origin, can support the survival of normal human plasma cells (PCs). PCs differentiate from plasmablasts (PBs) arising from activated B cells, essentially memory B cells. To study the survival of both PBs (C...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxn035

    authors: Geffroy-Luseau A,Jégo G,Bataille R,Campion L,Pellat-Deceunynck C

    更新日期:2008-06-01 00:00:00

  • IL-3 facilitates lymphocyte hexose transport by enhancing the intrinsic activity of the transport system.

    abstract::Interleukin 3 (IL-3) promotes the survival and proliferation of hematopoietic cells of various lineages in culture. Like most other hematopoietic colony stimulating factors, its mode of action is unknown. However, binding of the lymphokine induces protein tyrosine phosphorylation and enhanced glucose transport in some...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/3.8.827

    authors: Nefesh I,Bauskin AR,Alkalay I,Golembo M,Ben-Neriah Y

    更新日期:1991-08-01 00:00:00

  • Death by neglect as a deletional mechanism of peripheral tolerance.

    abstract::In contrast to most organs, the anatomy of the liver may allow naive CD8(+) T cells to make direct contact with liver parenchymal cells. We have previously shown, using a combination of TCR transgenic T cells specific for H-2 K(b) and hepatocytes expressing a transgenic H-2 K(b) molecule, that hepatocytes can induce a...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/11.8.1225

    authors: Bertolino P,Trescol-Biémont MC,Thomas J,Fazekas de St Groth B,Pihlgren M,Marvel J,Rabourdin-Combe C

    更新日期:1999-08-01 00:00:00

  • Gene expression profiles during human CD4+ T cell differentiation.

    abstract::To develop a comprehensive catalogue of phenotypic and functional parameters of human CD4(+) T cell differentiation stages, we have performed microarray gene expression profiling on subpopulations of human thymocytes and circulating naive CD4(+) T cells, including CD3(-)CD4(+)CD8(-) intrathymic T progenitor cells, CD3...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh112

    authors: Lee MS,Hanspers K,Barker CS,Korn AP,McCune JM

    更新日期:2004-08-01 00:00:00

  • T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes.

    abstract::Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The majo...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/9.11.1687

    authors: Bayrak S,Holmdahl R,Travers P,Lauster R,Hesse M,Dölling R,Mitchison NA

    更新日期:1997-11-01 00:00:00

  • Linomide, an immunomodulator that inhibits Th1 cytokine gene expression.

    abstract::Linomide (LS-2616, quinoline-3-carboxamide) has strong immunomodulating effects in animal models, inhibiting toxic shock, progressive autoimmune disease and cancer. In humans, linomide strongly reduced the appearance of new lesions in multiple sclerosis yet enhanced immune responses after bone marrow transplantation. ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/8.10.1603

    authors: Arad G,Katzenellenbogen M,Levy R,Slavin S,Kaempfer R

    更新日期:1996-10-01 00:00:00

  • Rearrangement and expression of kappa light chain genes can occur without mu heavy chain expression during differentiation of pre-B cells.

    abstract::The kinetics of kappa light (kappa L) chain gene rearrangement and expression on mRNA and protein level has been studied with four stromal cell/IL-7 reactive, long-term in vitro proliferating pre-B cell lines and clones, two from fetal liver of normal mice and two from fetal liver of E microH-bcl-2 transgenic (bcl-2-t...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.12.1609

    authors: Grawunder U,Haasner D,Melchers F,Rolink A

    更新日期:1993-12-01 00:00:00

  • Human CD8 co-receptor is strictly involved in MHC-peptide tetramer-TCR binding and T cell activation.

    abstract::Although there has been extensive analysis on the capacity of MHC-peptide tetramers to bind antigen-specific TCR, there have been comparatively few studies regarding the role of the CD4 and CD8 co-receptors in binding and activation by these multimeric molecules. Here, we start from the observation that different anti...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/14.1.39

    authors: Campanelli R,Palermo B,Garbelli S,Mantovani S,Lucchi P,Necker A,Lantelme E,Giachino C

    更新日期:2002-01-01 00:00:00

  • Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells.

    abstract::Naturally arising CD25(+)CD4(+) regulatory T (T(R)) cells can be exploited to establish immunologic tolerance to non-self antigens. In vivo exposure of CD25(+)CD4(+) T cells from normal naive mice to alloantigen in a T cell-deficient environment elicited spontaneous expansion of alloantigen-specific CD25(+)CD4(+) T(R)...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh122

    authors: Nishimura E,Sakihama T,Setoguchi R,Tanaka K,Sakaguchi S

    更新日期:2004-08-01 00:00:00