Journal of Cellular and Molecular Medicine · 2021 · 16 citations · 18 references
Life SciencesCell BiologyImmunologyApoptosisCellular ImmunologyImmunoregulationApoptosis In Immune CellsCell-mediated ImmunityT Cell ActivationT Cell BiologyT Cell Receptor SignalingCd8 Positive T CellsMediator Subunit Mutations
Abstract 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 α (IL‐7Rα), 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‐7Rα/STAT5 pathway‐mediated cell survival.
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