The microRNA miR-155 controls [CD8.sup.+] T cell responses by regulating interferon signaling

We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory [CD8.sup.+] T cells, but low miR-155 expression in naive and central memory cells. Antiviral [CD8.sup.+] T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to [CD8.sup.+] T cells, as miR-155-deficient [CD8.sup.+] T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral [CD8.sup.+] T cell responses in vivo. Gene-expression profiling showed that miR-155-deficient [CD8.sup.+] T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon-associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient [CD8.sup.+] T cells in vivo. We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and [CD8.sup.+] T cell responses to pathogens in vivo.