The CD8α-PILRa 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 CD8 alpha is critical for the maintenance of CD8(+) T cells in a physiologically quiescent state in peripheral lymphoid organs. Upon inducible deletion of CD8 alpha, both naive and memory CD8(+) T cells spontaneously acquired activation phenotypes and subsequently died without exposure to specific antigens. PILRa was identified as a ligand for CD8 alpha 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 CD8 alpha-PILR alpha interaction in the absence of antigen exposure.