Med1 Controls Cd8 T Cell Maintenance Through Il-7r-Mediated Cell Survival Signalling

Under steady-state conditions, the pool size of peripheral CD8(+) T cells is maintained through turnover and survival. Beyond TCR and IL-7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8(+) T cell proportion in spleens but not in thymi of mice with T cell-specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild-type (WT) and Med1-deficient CD8(+) T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1-deficient CD8(+) T cells compared with WT counterparts. Finally, Med1-deficient CD8(+) T cells exhibited a decreased expression of interleukin-7 receptor alpha (IL-7R alpha), down-regulation of phosphorylated-STAT5 (pSTAT5) and Bim up-regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8(+) T cells through IL-7R alpha/STAT5 pathway-mediated cell survival.