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

• 成果类型: Article
• 署名作者: Badr, Mohamed Elsherif; Zhang, Zhongmei; Tai, Xuguang; Singer, Alfred
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12498
• DOI: 10.1126/science.adh4124
• 发表日期: 2023-11-03
• 页码: 534-541
• 关键词: negative selection; clonal deletion; thymocyte apoptosis; lineage fate; expression; receptor; signal; alpha; identification; repertoire

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.