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.