Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
| Autor: | Melissa C. Ma, Hung-Sia Teh, Lisa C. Osborne, Jonathan W. Snow, M. Jill Miners, John J. Priatel, Ninan Abraham, Salim Dhanji, Mark A. Goldsmith |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell Survival Immunology CD8-Positive T-Lymphocytes Biology Article Mice 03 medical and health sciences Interleukin 21 0302 clinical medicine Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Interleukin-7 receptor Cells Cultured 030304 developmental biology Interleukin 3 Mice Knockout 0303 health sciences Receptors Interleukin-7 Interleukin Articles Molecular biology Mice Mutant Strains Mice Inbred C57BL Knockout mouse Mutagenesis Site-Directed Immunologic Memory CD8 Signal Transduction 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20061871 |
| Popis: | Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Ralpha, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Ralpha Y449XXM motif in mice by knock-in mutagenesis (IL-7Ralpha(449F)). Thymic precursors were reduced in number in IL-7Ralpha(449F) mice, but in marked contrast to IL-7Ralpha(-/-) knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Ralpha signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7Ralpha(449F) mice. Furthermore, we show that Bcl-2 is IL-7Ralpha Y449 independent and insufficient for IL-7-mediated maintenance of CD8 memory. |
| Databáze: | OpenAIRE |
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