[Analysis of gammac-dependent cytokines-mediated immunoregulation].
In the study of interleukin-2 (IL-2) -induced signal transduction system, we identified and cloned the third component of IL-2 receptor, IL-2Rgamma chain. Functional high affinity IL-2 receptor consists of three subunits, alpha, beta and gamma chains. Interestingly not only IL-2 but also IL-4, IL-7, IL-9, IL-15 and IL-21 utilize the gamma chain as an essential component of each receptors. Therefore the gamma chain is now called as a common gamma chain (gammac). Moreover the gene of gammac is on the X chromosome, and mutations of gammac gene cause human X-linked severe combined immunodeficiency (X-SCID) characterized by a complete or profound defect of T cells and NK cells, and by the presence of dysfunctional B cells. The dysfunctions in IL-7- and IL-15-induced signal transduction cause the T cell and NK cell defect, respectively and dysfunctions in both IL-4- and IL-21-induced signal transduction cause the B cell dysfunction in X-SCID patients. Gene therapy is a good candidate for X-SCID treatment because only the HLA-matched bone marrow transplantation is an effective therapy. Unfortunately because of an unexpected adverse effect, such gene therapy using retrovirus vector is now aborted. IL-21 is a recently identified cytokine, which shares the gammac. IL-21 regulates the proliferation of T cells, the proliferation and differentiation of B cells, and the activation and expansion of NK cells. We demonstrated that human IL-21 was produced from activated CD4+ central and effector memory T cells but not from naive CD4+ T cells nor CD8+ T cells. Furthermore we found that IL-21 supported cytokine-driven proliferation of CD4+ helper T cells cooperatively with IL-7 and IL-15.
Asao
Hironobu
H
Department of Immunology, Yamagata University Faculty of Medicine, Yamagata.
D000818:Animals; D015316:Genetic Therapy; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000502:physiology*; D007378:Interleukins / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology*; D009154:Mutation; D015375:Receptors, Interleukin-2; D053632:X-Linked Combined Immunodeficiency Diseases / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D000098546:Interleukin-21
D053631:Interleukin Receptor Common gamma Subunit; D007378:Interleukins; D015375:Receptors, Interleukin-2; D000098546:Interleukin-21