Jak3 binds to the y common chain of the IL-2 family of cytokine receptors, whose signals are obligatory for lymphocyte development. Not unexpectedly, disruption of Jak3 in mice resulted in severe perturbations in lymphocyte development caused predominantly by defects in IL-7 signaling (6-8), analogous to that observed in y common chain-deficient mice (9,10). In addition, a patient with mutations in both copies of the Jak3 allele displayed severe combined immunodeficiency (11). B-cell development was blocked at the pre-B-cell stage, and T-lymphocyte development was severely affected, resulting in a reduction in thymic size and cellularity. Proliferation of Jak3-deficient T-cells was blunted in response to various mitogenic stimuli including IL-2, IL-4, IL-7, lipopolysaccharide (LPS), and activation of the T-cell receptor and T-cell co-receptor, CD28.

0 0

Post a comment