CTLA-4 regulates induction of anergy in vivo
CTLA-4 regulates induction of anergy in vivo
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DOI：
10.1016/s1074-7613(01)00097-8
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发表时间：
2001-02-01
期刊：
影响因子：
32.4
通讯作者：
Sharpe, AH
中科院分区：
文献类型：
--
作者：
Greenwald, RJ;Boussiotis, VA;Sharpe, AH
利用缺乏CTLA-4的幼稚TCR转基因T细胞，研究了在体内诱导外周T细胞耐受过程中对CTLA-4的需求。CTLA-4(-/-) T细胞对耐受性诱导具有抗性，其增殖反应、IL-2的产生和进入细胞周期的进展证明了这一点。在体内暴露于耐受性刺激和体外再刺激后，野生型T细胞在细胞周期的G1晚期到S限制点被阻断。相反，CTLA-4(-/-) T细胞进入细胞周期的S期，表现为p27（kip1）下调、cdk2激酶活性升高和Rb过度磷酸化。因此，CTLA-4在决定T细胞遭遇耐受性刺激的结果中起着至关重要的作用。
The requirement for CTLA-4 during the induction of peripheral T cell tolerance in vivo was investigated using naive TCR transgenic T cells lacking CTLA-4. CTLA-4(-/-) T cells are resistant to tolerance induction, as demonstrated by their proliferative responses, IL-2 production, and progression into the cell cycle. Following exposure to a tolerogenic stimulus in vivo and restimulation in vitro, wild-type T cells are blocked at the late G1 to S restriction point of the cell cycle. In contrast, CTLA-4(-/-) T cells enter into the S phase of the cell cycle, as shown by downregulation of p27(kip1), elevated cdk2 kinase activity, and Rb hyperphosphorylation. Thus, CTLA-4 has an essential role in determining the outcome of T cell encounter with a tolerogenic stimulus.