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Departments of
*
Cancer Biology and
Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195; and
Institute of Molecular Biology, University of Zurich, Honggerberg, Zurich, Switzerland
The IFN-induced and dsRNA-activated kinase (PKR) mediates the
antiviral and antiproliferative effects of IFN-
and IFN-
. Despite
these findings, Pkr-/- mice have no
overt immunological phenotype. Here we tested the role of PKR in
cellular 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.
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