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 cytokine receptors using the common gamma-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.
Thomis
D C
DC
Department of Pathology, University of Massachusetts Medical School, Center for Blood Research, Boston, MA 02115, USA.
Aramburu
J
J
Berg
L J
LJ
D000818:Animals; D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D007399:Interphase / Q000235:genetics / Q000276:immunology; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3