Negative Regulation of CD8+ T Cell Function by the IFN-Induced and Double-Stranded RNA-Activated Kinase PKR

Abstract

The IFN-induced and dsRNA-activated kinase (PKR) mediates the antiviral and antiproliferative effects of IFN-α and IFN-γ. Despite these findings, Pkr‾⁄‾ mice have no overt immunological phenotype. Here we tested the role of PKR in llular immunity by determining the induction and elicitation of contact hypersensitivity in Pkr‾⁄‾ mice, a model of T cell-mediated immunity. When compared with wild type, the magnitude of contact hypersensitivity responses in Pkr‾⁄‾ mice were 2-fold higher and of extended duration. 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 defect intrinsic to the CD8+ T cell population. Isolated lymph node T cells from Pkr‾⁄‾ mice were hyperproliferative during Con A-mediated stimulation. 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.