The CD8α–PILRα interaction maintains CD8 ⁺ T cell quiescence

Abstract

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.

TRIB2 safeguards naive T cell homeostasis during aging

“…However, naive CD8 + T cells engage PILRα, a ligand for CD8α, as a safekeeping mechanism to counteract spontaneous activation and cell death. 38 …”

Construction of regulatory network for alopecia areata progression and identification of immune monitoring genes based on multiple machine-learning algorithms

“…29–31 CD8A is the surface glycoprotein of most cytotoxic T lymphocytes and mediates mutual recognition between cells in the immune system. 32 CD2 is the surface antigen of all peripheral blood T cells and has the effect of immune recognition. 33 GZMA and PRF1 are common components necessary for cytotoxic T lymphocytes and natural killer cells to lysis target cells.…”

Targets of tumor microenvironment for potential drug development

“…CD8 + T cell quiescence is fundamental for cell survival and repertoire diversity. Zheng and colleagues discovered that the cell surface CD8α–PILRα interaction between T cell‐myeloid cell crosstalk maintains CD8 + T cell quiescence by showing that inducible deletion of CD8α in mice results in a loss of both naïve CD8 + T cells and Tm cell quiescence, 26 suggesting that disrupting the interaction can enhance the transition from Tm to activated CD8 + T cells. Huang and colleagues demonstrated the distinct functional states of responsible CD8 + T cells in tumor‐draining lymph nodes (TDLN), where TCF‐1 + TOX − CD8 + T cells were bona fide Tm cells that function as real responders of the PD‐1/PD‐L1 immune checkpoint blockade (ICB), which can be harnessed to potentiate antitumor immunotherapy 27 .…”