Image_1_Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival.jpeg

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.