T cell development and activation in Jak3-deficient mice
Department of Pathology
Animals; Humans; Janus Kinase 3; Lymphocyte Activation; Mice; Mice, Knockout; Protein-Tyrosine Kinases; T-Lymphocytes
Life Sciences | Medicine and Health Sciences
Jak3, a member of the Janus family of tyrosine kinases, participates in signaling through cytokine receptors that contain the common gamma-chain, including the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15. Jak3- and gamma c-deficient mice have pleiotropic defects that can be attributed to their inability to respond to multiple specific cytokines. A great deal of recent work has focused on the T cell defects in these mutant mice. Specifically, Jak3- and gamma c-deficient mice have small thymuses revealing a defect in T cell development, and in addition, have functionally unresponsive peripheral T cells with an activated/memory cell phenotype. The thymic defect in these mutant mice strongly resembles that seen in IL-7 and IL-7 receptor knockout mice, suggesting that the lack of IL-7 receptor signaling accounts for this defect in Jak3-/- and gamma c- mice. To characterize this defect further, we have examined the earliest stages of T cell development in adult and fetal Jak3-/- thymuses. These studies identify two discrete developmental defects at the CD4-CD8- stage of T cell maturation. Analyses of peripheral T cells in Jak3-/- and gamma c- mice have also revealed a number of abnormalities. All of the T cells in these mutant mice have an activated phenotype and a large fraction of them are proliferating in vivo. In addition, Jak3-/- and gamma c- T cells are more prone to undergo apoptosis than wild-type T cells. Together, these features account for the decreased IL-2 secretion by in vitro-stimulated Jak3-/- T cells. Overall, many of the lymphoid defects of Jak3- and gamma c-deficient mice can be accounted for by the lack of IL-7R and IL-2R signaling; however, other cytokine systems must also be involved in maintaining peripheral T cell homeostasis.
DOI of Published Version
J Leukoc Biol. 1998 Jun;63(6):669-77.
Journal of leukocyte biology
Baird, Allison Michelle; Thomis, Daniel C.; and Berg, Leslie J., "T cell development and activation in Jak3-deficient mice" (1998). Open Access Articles. 1142.