Crucial role of Jak3 in negative selection of self-reactive T cells.
Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL-2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in mice and humans. In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age. However, we found that self-reactive T cells were not deleted in the thymus and the peripheral tissues in Jak3-deficient mice. All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca2+ response upon T cell receptor (TCR) stimulation. From the analysis of TCR-transgenic Jak3-deficient mice, only self-reactive T cells appeared to be in the activated state and anergic. These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells.
Saijo
K
K
Center for Biomedical Science, Chiba University School of Medicine, Inohana, Chuo-ku, Japan.
Park
S Y
SY
Ishida
Y
Y
Arase
H
H
Saito
T
T
D000818:Animals; D006801:Humans; D053616:Janus Kinase 3; D008212:Lymphocyte Depletion; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3