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.

T cell development and activation in Jak3-deficient mice.

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.

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.

The role of Jak3 in lymphoid development, activation, and signaling.

Mutations in a number of lymphoid signaling molecules lead to immunodeficiencies in mice and humans. Among these, one very pleiotropic syndrome results from deficiencies in an array of cytokine signaling pathways utilizing a cytokine receptor common gamma chain, gammac, and the tyrosine kinase Jak3. Recent advances in our understanding of the role of gammac and Jak3 in lymphocyte development and function highlight the importance of cytokine receptor signaling pathways in regulating lymphoid homeostasis and responsiveness.