T cells from Jak3-deficient mice have intact TCR signaling, but increased apoptosis.
The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine receptors utilizing the common gamma-chain (gamma(c)). Mice and humans lacking Jak3 have severe immune deficiencies, including defects in B and T lymphocyte development and function. In particular, Jak3-deficient mice have mature T cells with an activated phenotype, yet these cells are functionally nonresponsive. In this work, we show that Jak3-deficient T cells have no gross defects in early T cell signaling, as measured by TCR-induced tyrosine phosphorylation and calcium mobilization responses. Furthermore, we find that Jak3-deficient mice expressing a transgenic TCR have extremely low numbers of peripheral T cells with a naive phenotype, indicating that both peripheral activation and expansion of Jak3-/- T cells are driven by antigenic signals. We show that, similar to gamma(c)-deficient mice, T cells from Jak3-deficient mice have an increased susceptibility to apoptosis. Previously, we showed that when stimulated in vitro by CD3 plus CD28 cross-linking, Jak3-/- T cells secrete greatly reduced amounts of IL-2, and fail to proliferate. However, by measuring intracellular IL-2 levels, we find that Jak3-/- T cells produce amounts of IL-2 similar to activated T cells from control mice, further supporting the notion that there is no defect in TCR signaling in Jak3-/- T cells.
Thomis
D C
DC
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Lee
W
W
Berg
L J
LJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3