文章基本信息

标题：CD154 is a negative regulator of autoaggressive CD8+ T cells in type 1 diabetes
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作者：Catrin M. McGregor ; Stephen P. Schoenberger ; E. Allison Green 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：25
页码：9345-9350
DOI：10.1073/pnas.0402807101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：TNF/CD80 mice, a CD8+ T cell-mediated model for type 1 diabetes, transgenically express tumor necrosis factor {alpha} (TNF-{alpha}) and the costimulatory molecule CD80 in their pancreatic islets. Here we show that these molecules bypass the need for CD40-CD154 costimulatory interactions in activation of CD8+ T cells, allowing us to determine the role of CD40-CD154 signals in regulation of autoaggressive CD8+ T cells after their in vivo priming. TNF/CD80 CD154-deficient mice rapidly develop diabetes, whereas CD154-sufficient mice do not. This finding correlates with the decreased numbers of CD4+CD25+ T regulatory (TR) cells in the islets and pancreatic lymph nodes, in comparison to disease-protected CD154-sufficient mice. Administration of a CD40 agonistic antibody induces a systemic and tissue-specific increase in TR cells. However, this increase fails to delay diabetes development in the absence of CD154. Adoptive transfer studies show that CD8+ T cells from TNF/CD80 CD154-deficient, but not CD154-sufficient, mice are resistant to regulation in vivo. This study provides evidence that CD40-transduced signals initiate TR cell increase in vivo and that CD154-transduced signals sensitize autoaggressive CD8+ T cells to suppression.