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 (gammac), 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+, gammadelta, 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.
Thomis
D C
DC
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Berg
L J
LJ
D000818:Animals; D006720:Homozygote; D006801:Humans; D016130:Immunophenotyping; D053616:Janus Kinase 3; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3