| First Author | Baird AM | Year | 1998 |
| Journal | J Leukoc Biol | Volume | 63 |
| Issue | 6 | Pages | 669-77 |
| PubMed ID | 9620658 | Mgi Jnum | J:47917 |
| Mgi Id | MGI:1206231 | Doi | 10.1002/jlb.63.6.669 |
| Citation | Baird AM, et al. (1998) T cell development and activation in Jak3-deficient mice. J Leukoc Biol 63(6):669-77 |
| abstractText | 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. |
