期刊
JOURNAL OF IMMUNOLOGY
卷 168, 期 3, 页码 1190-1197出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.168.3.1190
关键词
-
类别
资金
- NIAID NIH HHS [R01 AI 34824, P01 AI 35296] Funding Source: Medline
CD8 T cells undergo autocrine IL-2-dependent proliferation upon TCR engagement and costimulation, but within 3-4 days, they become activation-induced nonresponsive (AINR) and display a split anergy. They can lyse targets and secrete IFN-gamma but they cannot produce IL-2 in response to TCR ligation and costimulation, due at least in part to an inability to up-regulate mitogen-activated protein kinases and IL-2 mRNA. Exogenous IL-2 can drive continued proliferation of AINR cells and nonresponsiveness is reversed within 1-2 days so that Ag-driven proliferation can resume. Mitogen-activated protein kinases and IL-2 mRNA can again be up-regulated, but rewiring' has occurred so that these events no longer depend upon costimulation; TCR engagement is sufficient. Development of AINR appears to be a normal part of the differentiation program of CD8 T cells, providing a regulatory checkpoint to convert the initial helper-independent response to one that depends upon CD4 T cell help for continued expansion of the effector CTL. Once permission is given, in the form of IL-2, to pass this checkpoint, the CTL can make a prolonged response to persisting Ag in the absence of further CD4 T cell help.
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