Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Yale College, Yale University, New Haven, CT, USA.
Science. 2022 May 27;376(6596):996-1001. doi: 10.1126/science.aaz8658. Epub 2022 May 26.
T cell quiescence is essential for maintaining a broad repertoire against a large pool of diverse antigens from microbes and tumors, but the underlying molecular mechanisms remain largely unknown. We show here that CD8α is critical for the maintenance of CD8 T cells in a physiologically quiescent state in peripheral lymphoid organs. Upon inducible deletion of CD8α, both naïve and memory CD8 T cells spontaneously acquired activation phenotypes and subsequently died without exposure to specific antigens. PILRα was identified as a ligand for CD8α in both mice and humans, and disruption of this interaction was able to break CD8 T cell quiescence. Thus, peripheral T cell pool size is actively maintained by the CD8α-PILRα interaction in the absence of antigen exposure.
T 细胞静止对于维持针对微生物和肿瘤的大量多样化抗原的广泛 repertoire 至关重要，但潜在的分子机制在很大程度上仍不清楚。我们在这里表明，CD8α 对于维持外周淋巴器官中 CD8 T 细胞的生理静止状态至关重要。在诱导性缺失 CD8α 后，幼稚和记忆 CD8 T 细胞自发获得激活表型，随后在没有接触到特定抗原的情况下死亡。PILRα 被鉴定为小鼠和人类中 CD8α 的配体，破坏这种相互作用能够打破 CD8 T 细胞静止。因此，在没有抗原暴露的情况下，CD8α-PILRα 相互作用积极维持外周 T 细胞库的大小。
