Cutting edge: an alternative pathway of CD4+ T cell differentiation is induced following activation in the absence of gamma-chain-dependent cytokine signals.
This report addresses the role of gamma-chain cytokine signals in regulating CD4(+) T cell differentiation following activation. Using murine CD4(+) T cells lacking the Jak3 tyrosine kinase, we show that activation of these cells in the absence of gamma-chain-dependent cytokine signals induces an alternative pathway of T cell differentiation. Specifically, activated Jak3(-/-) CD4(+) T cells produce IL-10, TGF-beta, and IFN-gamma, but not IL-2 or IL-4, and are unable to proliferate in vitro. In addition, Jak3(-/-) CD4(+) T cells express high levels of programmed death-1 and lymphocyte activation gene-3 and modestly suppress the proliferation of wild-type CD4(+) T cells in coculture assays. Together, these features demonstrate a striking similarity between Jak3(-/-) CD4(+) T cells and the regulatory T cells that have been shown to suppress immune responses in vitro and in vivo. We conclude that Jak3 is a critical component of signaling pathways that regulate T cell differentiation into effector vs regulatory lineages.
Mayack
Shane R
SR
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Berg
Leslie J
LJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3