美国国立卫生研究院Alfred Singer小组宣布他们的论文发现了揭开CD8谱系决定表明功能不同的CD8⁺ T细胞是由不同的MHC-I胸腺肽选择的。相关论文于2026年1月19日发表于国际顶尖学术期刊《自然—免疫学》杂志上。

该课题组研究人员现在报道，在Cd4和CD8基因位点编码CD8共受体可调节主要组织相容性复合体（MHC-I） I类T细胞抗原受体信号传导持续时间，以产生所有潜在的CD8⁺ T细胞亚群。引人注目的是，这些小鼠揭示了功能不同的CD8⁺ T细胞被不同的MHC-I胸腺肽选择。由胸腺蛋白酶体产生的仅在胸腺皮层表达的β5t肽信号传导的胸腺细胞总是成为细胞毒性CD8⁺ T细胞，这表明当胸腺细胞离开皮层时，它们的信号传导停止；而由非β5t肽信号传导的胸腺细胞在整个胸腺中表达成为辅助或先天记忆CD8⁺ T细胞，因为它们的信号在皮层外持续或复发。因此，不同的MHC-I肽选择不同功能的CD8⁺ T细胞，在阳性选择和胸腺细胞迁移过程中整合肽特异性和CD8⁺ T细胞功能，正是由于其胸腺分布的不同。

据介绍，由T细胞抗原受体发出信号进行正向选择的胸腺细胞在通过胸腺迁移时获得不同的功能命运，但这是如何发生的仍不清楚。

附：英文原文

Title: Unraveling CD8 lineage decisions reveals that functionally distinct CD8+ T cells are selected by different MHC-I thymic peptides

Author: Shinzawa, Miho, Ramos, Nicole, Bui, Khanh, Hajjar, William, Crossman, Assiatu, Chen, Xiongfong, Cam, Margaret, Takahama, Yousuke, Singer, Alfred

Issue&Volume: 2026-01-19

Abstract: Thymocytes signaled by T cell antigen receptors to undergo positive selection acquire different functional fates while migrating through the thymus, but how this occurs remains uncertain. We now report that encoding CD8 co-receptors in both Cd4 and Cd8 gene loci modulates major histocompatibility complex (MHC-I) class I T cell antigen receptor signaling duration to generate all potential CD8+ T cell subsets. Strikingly, such mice revealed that functionally different CD8+ T cells are selected by different MHC-I thymic peptides. Thymocytes signaled by β5t-peptides produced by thymoproteasomes exclusively expressed in the thymic cortex invariably become cytotoxic CD8+ T cells indicating their signaling ceases when thymocytes leave the cortex; whereas thymocytes signaled by nonβ5t-peptides expressed throughout the thymus become either helper or innate memory CD8+ T cells because their signaling persists or recurs outside the cortex. Thus, it is because of their different thymic distributions that different MHC-I peptides select functionally different CD8+ T cells, integrating peptide specificity and CD8+ T cell function during positive selection and thymocyte migration.

DOI: 10.1038/s41590-025-02411-4

Source: https://www.nature.com/articles/s41590-025-02411-4