研究人员表示，CD8 T细胞耐受性被认为是自体反应性胸腺细胞在胸腺中分化成成熟的CD8 T细胞之前克隆性删除的结果。
然而，研究人员报告说，在小鼠体内，CD8 T细胞耐受性是由未成熟的自体活性CD8胸腺细胞过早被胸腺驱逐到外周，在那里分化成自我耐受的成熟CD8 T细胞。胸腺过早驱逐是由T细胞受体（TCR）驱动的转录抑制因子Gfi1的下调触发的，Gfi1会诱导鞘磷脂-1-磷酸受体-1（S1P1）在负选的未成熟CD8胸腺细胞上的表达。因此，胸腺过早驱逐是CD8 T细胞耐受性的基础，也是胸腺中不存在的带有自反应TCR的成熟CD8 T细胞在外周出现的机制。
附：英文原文
Title: CD8 T cell tolerance results from eviction of immature autoreactive cells from the thymus
Author: Mohamed Elsherif Badr, Zhongmei Zhang, Xuguang Tai, Alfred Singer
Issue&Volume: 2023-11-03
Abstract: 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.
DOI: adh4124
Source: https://www.science.org/doi/10.1126/science.adh4124