CD8 T cell tolerance results from eviction of immature autoreactive cells from the thymus

被引：15

作者：

Badr, Mohamed Elsherif ^{[1
]}

Zhang, Zhongmei ^{[1
]}

Tai, Xuguang ^{[1
]}

Singer, Alfred ^{[1
]}

机构：

[1] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE | 2023年 / 382卷 / 6670期

基金：

美国国家卫生研究院;

关键词：

NEGATIVE SELECTION; CLONAL DELETION; THYMOCYTE APOPTOSIS; LINEAGE FATE; EXPRESSION; RECEPTOR; SIGNAL; ALPHA; IDENTIFICATION; REPERTOIRE;

D O I：

10.1126/science.adh4124

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CD8 T cell tolerance is thought to result from clonal deletion of autoreactive thymocytes before they differentiate into mature CD8 T cells in the thymus. However, we report that, in mice, CD8 T cell tolerance instead results from premature thymic eviction of immature autoreactive CD8 thymocytes into the periphery, where they differentiate into self-tolerant mature CD8 T cells. Premature thymic eviction is triggered by T cell receptor (TCR)-driven down-regulation of the transcriptional repressor Gfi1, which induces expression of sphingosine-1-phosphate receptor-1 (S1P1) on negatively selected immature CD8 thymocytes. Thus, premature thymic eviction is the basis for CD8 T cell tolerance and is the mechanism responsible for the appearance in the periphery of mature CD8 T cells bearing autoreactive TCRs that are absent from the thymus.

引用

页码：534 / 541

页数：8

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