Peripheral Expression of Jak3 Is Required to Maintain T Lymphocyte Function

The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine receptors that utilize the common γ chain (γ_c), such as those for IL-2, IL-4, IL-7, IL-9, and IL-15. Recent studies of Jak3-deficient mice and humans have demonstrated that Jak3 plays a critical role in B and T lymphocyte maturation and function. The T lymphocyte defects in Jak3-deficient mice include a small thymus, a decrease in peripheral CD8⁺ cells, an increase in the surface expression of activation markers, and a severe reduction in proliferative and cytokine secretion responses to mitogenic stimuli. To determine whether the peripheral T lymphocyte defects result from aberrant maturation in the thymus or from the absence of Jak3 protein in peripheral T cells, we generated reconstituted mice that express normal levels of Jak3 protein in the thymus but lose Jak3 expression in peripheral T cells. Jak3 expression in the thymus restores normal T cell development, including CD8⁺, γδ, and natural killer cells. However, the loss of Jak3 protein in peripheral T cells leads to the Jak3^−/− phenotype, demonstrating that Jak3 is constitutively required to maintain T cell function.