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 gamma chain (gamma(c)), su ch as those for IL-2, IL-4, IL-7, IL-9, and IL-15. Recent studies of J ak3-deficient mice and humans have demonstrated that Jak3 plays a crit ical role in B and T lymphocyte maturation and function. The T lymphoc yte defects in Jak3-deficient mice include a small thymus, a decrease in peripheral CD8(+) cells, an increase in the surface expression of a ctivation markers, and a severe reduction in proliferative and cytokin e secretion responses to mitogenic stimuli. To determine whether the p eripheral T lymphocyte defects result from aberrant maturation in the thymus or from the absence of Jak3 protein in peripheral T cells, we g enerated reconstituted mice that express normal levels of Jak3 protein in the thymus but lose Jak3 expression in peripheral T cells. Jak3 ex pression in the thymus restores normal T cell development, including C D8(+), gamma delta, and natural killer cells. However, the loss of Jak 3 protein in peripheral T cells leads to the Jak3(-/-) phenotype, demo nstrating that Jak3 is constitutively required to maintain T cell func tion.