期刊
JOURNAL OF IMMUNOLOGY
卷 185, 期 1, 页码 357-366出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000066
关键词
-
类别
资金
- Natural Sciences and Engineering Research Council (Canada)
- Canadian Institutes for Health Research [MOP-86530]
- The Centre de Recherche Clinique Etienne-Le Bel du Centre Hospitalier Universitaire de Sherbrooke
- Fonds de la Recherche en Sante' Quebec
We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity. In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes. In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag. Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice. SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation. Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines. Cytokine-driven homeostatic expansion in lymphopenic RIP-GP mice allowed SOCS1-null, but not wild-type, P14 cells to exert their pathogenic potential even without Ag stimulation. These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags. The Journal of Immunology, 2010, 185: 357-366.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据