The CD8α–PILRα interaction maintains CD8 ⁺ T cell quiescence

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.