MicroRNA-155 controls CD8(+) T cell responses by regulating interferon signaling

We show that microRNA-155 (miR-155) is upregulated in primary effector and effector memory CD8(+) T cells but is low in naive and central memory cells. Anti-viral CD8(+) T cell responses and viral clearance were impaired in miR-155 deficient (miR-155-KO) mice, and this defect was intrinsic to CD8(+) T cells as miR-155-KO CD8(+) T cells mounted greatly reduced primary and memory responses. Conversely, miR-155 overexpression augmented anti-viral CD8(+) T cell responses in vivo. Gene expression profiling of miR-155-KO CD8(+) T cells revealed increased type I interferon signaling and sensitivity. Inhibiting STAT1 or IRF7 increased miR-155-KO CD8(+) T cell responses in vivo. We report a novel role for miR-155 in regulating IFN responsiveness and CD8(+) T cell responses against pathogens in vivo.