Negative regulation of CD8(+) T cell function by the IFN-induced and double-stranded RNA-activated kinase PKR

The IFN-induced and dsRNA-activated kinase (PKR) mediates the antiviral and antiproliferative effects of IFN-alpha and IFN-gamma Despite these finding s, Pkr(-/-) mice have no overt immunological phenotype, Here we tested the role of PKR in cellular immunity by determining the induction and elicitati on of contact hypersensitivity in Pkr(-/-) mice, a model of T cell-mediated immunity, When compared with wild type, the magnitude of contact hypersens itivity responses in Pkr(-/-) mice were a-fold higher and of extended durat ion. This was also observed when naive recipients of immune CD8(+) T cells from sensitized Pkr(-/-) and CD4(+) T cells from sensitized wild-type Pkr(/+) or Pkr(-/-) mice were challenged with hapten, indicating a regulatory d efect intrinsic to the CD8(+) T cell population. Isolated lymph node T cell s from Pkr-/- mice mere hyperproliferative during Con A-mediated stimulatio n. These results implicate PKR for the first time in the growth control of mature T lymphocytes and give insight into the negative regulation of CD8() T cell-mediated immune responses.