Cutting edge: an alternative pathway of CD4+ T cell differentiation is induced following activation in the absence of gamma-chain-dependent cytokine signals
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2006-02-04Keywords
AnimalsCD4-Positive T-Lymphocytes
*Cell Differentiation
Cell Proliferation
Cells, Cultured
Cytokines
DNA-Binding Proteins
Homeostasis
Janus Kinase 3
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Protein-Tyrosine Kinases
*Signal Transduction
Thymus Gland
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2006 Feb 15;176(4):2059-63.
DOI
10.4049/jimmunol.176.4.2059Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38209PubMed ID
16455959Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.176.4.2059