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Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease
We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28- B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1996
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192532/ https://www.ncbi.nlm.nih.gov/pubmed/8666905 |
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collection | PubMed |
description | We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28- B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40- L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2- associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium. |
format | Text |
id | pubmed-2192532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1996 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21925322008-04-16 Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease J Exp Med Articles We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28- B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40- L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2- associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium. The Rockefeller University Press 1996-04-01 /pmc/articles/PMC2192532/ /pubmed/8666905 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease |
title | Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease |
title_full | Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease |
title_fullStr | Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease |
title_full_unstemmed | Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease |
title_short | Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease |
title_sort | distinct regulatory roles of lymphocyte costimulatory pathways on t helper type-2 mediated autoimmune disease |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192532/ https://www.ncbi.nlm.nih.gov/pubmed/8666905 |