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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

Gamma c cytokines condition the progressive differentiation of CD4+ T cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 12 Sep 2007

Masse GX, Corcuff E, Strick-Marchand H, Guy-Grand D, Tafuri-Bladt A, Albert ML, Lantz O, Di Santo JP

Link to Pubmed [PMID] – 17855567

Proc. Natl. Acad. Sci. U.S.A. 2007 Sep;104(39):15442-7

After their initial antigen encounter in the secondary lymphoid organs, activated T cells must receive additional signals in the peripheral tissues to fully differentiate. Here, we provide evidence that gamma(c) cytokines are critical during this process. Using the Marilyn (Ml) T cell antigen receptor (TCR) transgenic model, we show that male skin grafts are tolerated in the absence of gamma(c), but that Ml CD4(+) T cells proliferate normally in response to antigen, traffic to the graft site and recruit an inflammatory response [including natural killer (NK) cells, neutrophils, and macrophages] that is independent of T cell gamma(c) expression. Whereas wild-type T cells demonstrate a progressive differentiation phenotype from the spleen to the tissues, skin-infiltrating effector T cells (CD44(hi)CD62L(lo)) from gamma(c)(-) mice were phenotypically abnormal with reduced ICOS, NKG2D, granzyme B, and IFN-gamma expression. These defects could be mapped to deficiencies in IL-2 and, surprisingly, IL-15. These results define a late checkpoint in T cell differentiation in the tissues where gamma(c) cytokines, including IL-15, authenticate CD4(+) T cell effector functions.

http://www.ncbi.nlm.nih.gov/pubmed/17855567