The Jak family tyrosine kinase Jak3 is required for IL-2 synthesis by naive/resting CD4(+) T cells

The Jak family tyrosine kinase, Jak3, is involved in signaling through cyto kine receptors using the common gamma-chain. Mice deficient in Jak3 have ma ture T cells, all of which have an activated/memory cell phenotype but are unresponsive to in vitro stimulation Due to this activated phenotype, it ha s been impossible to determine whether Jak3 plays a role in the responsiven ess of naive/resting T cells. To circumvent this difficulty, we generated n aive/resting Jak3-negative T cells by two genetic approaches. After stimula tion, these cells failed to produce significant amounts of IL-2, Although n o signaling defect could be detected, we did find that naive/resting Jak3-n egative T cells have substantially reduced levels of the transcription fact or 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 require d to maintain the normal levels of basal transcription factors required for immediate responsiveness to Ag activation.