Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival.

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4 T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4 T cells but up-regulated in CD8 T cells. CD4 and CD8 T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4 T cells. Transcriptome analysis of CD4 T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4 T cells, but not in bystander CD4 nor in CD8 T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150 antigen-specific CD4 T. Thus, miR-150 impacts CD4 T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.