Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling

J Cell Mol Med. 2021 May;25(10):4870-4876. doi: 10.1111/jcmm.16465. Epub 2021 Mar 17.

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.

Keywords: CD8+ T cells; IL-7R signalling; Med1; apoptosis; homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow Cells
  • CD8-Positive T-Lymphocytes* / cytology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Mediator Complex Subunit 1 / genetics
  • Mediator Complex Subunit 1 / immunology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Interleukin-7 / immunology*
  • Signal Transduction
  • Spleen / cytology
  • Spleen / immunology*

Substances

  • Med1 protein, mouse
  • Mediator Complex Subunit 1
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain