| First Author | Lee JM | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 5 | Pages | 3155-64 |
| PubMed ID | 15322176 | Mgi Jnum | J:92705 |
| Mgi Id | MGI:3054319 | Doi | 10.4049/jimmunol.173.5.3155 |
| Citation | Lee JM, et al. (2004) IL-15Ralpha is a negative regulator of TCR-activated proliferation in CD4+ T cells. J Immunol 173(5):3155-64 |
| abstractText | Although IL-15 is known to be a T cell growth factor, the function in T cells of IL-15Ralpha, its high affinity receptor, remains unclear. We found that murine IL-15Ralpha(-/-) CD4(+) T cells hyperproliferated in response to TCR stimulation, in vitro and in vivo, and displayed a lower TCR activation threshold than wild-type CD4(+) T cells. TCR-induced activation of Zap70 and of the phospholipase C-gamma1-NFATp, Ras-ERK-c-Fos, and Rac-JNK-c-Jun pathways was all augmented in IL-15Ralpha(-/-) CD4(+) T cells. This in turn led to earlier IL-2Ralpha induction and higher IL-2 production, which most likely contribute to the hyperproliferation of IL-15Ralpha(-/-) CD4(+) T cells. Exogenous IL-15 reduced levels of TCR-activated signals, transcription factors, IL-2, and IL-2Ralpha, and division in wild-type CD4(+) T cells. These results reveal IL-15Ralpha to be a negative regulator for CD4(+) T cell activation and demonstrate a novel layer of regulation of TCR signaling by a cytokine system. |
