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Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and
Center for Blood Research, Boston, MA 02115
The Jak family tyrosine kinase, Jak3, is involved in signaling
through cytokine receptors using the common
-chain. Mice deficient
in Jak3 have mature T cells, all of which have an activated/memory cell
phenotype but are unresponsive to in vitro stimulation. Due to this
activated phenotype, it has been impossible to determine whether Jak3
plays a role in the responsiveness of naive/resting T cells. To
circumvent this difficulty, we generated naive/resting Jak3-negative T
cells by two genetic approaches. After stimulation, these cells failed
to produce significant amounts of IL-2. Although no signaling defect
could be detected, we did find that naive/resting Jak3-negative T cells
have substantially reduced levels of the transcription factor NF-AT1
and moderately reduced levels of c-Jun and c-Fos. On the basis of these
data, we propose that Jak3-dependent cytokine signals may be required
to maintain the normal levels of basal transcription factors required
for immediate responsiveness to Ag activation.
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