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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Di Santo, James P. Masse, Guillemette X. Tafuri-bladt, Anna Strick-marchand, Hélène Guy-grand, Delphine Albert, Matthew L. Lantz, Olivier Corcuff, Erwan |
| Description | Author Affiliation: Masse GX ( Cytokines and Lymphoid Development Unit, Immunology Department, Institut Pasteur, F-75724 Paris, France.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 39 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD4-Positive T-Lymphocytes Metabolism Cell Differentiation Cytokines Animals Antigens, CD44 Biosynthesis Granzymes Interferon-gamma Interleukin-15 Interleukin-2 Receptor Beta Subunit L-Selectin Mice Mice, Transgenic NK Cell Lectin-Like Receptor Subfamily K Receptors, Immunologic Receptors, Natural Killer Cell Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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