LAUSR

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. Description CD8α keeps T cells humming along In addition to acting as a T cell lineage marker, the CD8 heterodimer acts as a co-receptor to enhance T cell receptor (TCR) signaling after antigen stimulation. Whether CD8 plays any other antigen-independent functions is unclear. Zheng et al. found that inducible deletion of CD8α in mice resulted in a loss of both naïve and memory CD8 T cell quiescence, which is essential for their survival and repertoire diversity. Quiescence is actively maintained by T cell–myeloid cell cross-talk through cell surface CD8α –PILRα interactions. Disruption of this interaction leads to spontaneous activation and subsequent loss of naïve and memory CD8+ T cell pools in peripheral lymphoid organs. —STS CD8α participates in the maintenance of T cell homeostasis through its interaction with the paired immunoglobulin-like type 2 receptor α.