| First Author | Chen S | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 8 | Pages | 2229-40 |
| PubMed ID | 18624295 | Mgi Jnum | J:138564 |
| Mgi Id | MGI:3805411 | Doi | 10.1002/eji.200838167 |
| Citation | Chen S, et al. (2008) Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells. Eur J Immunol 38(8):2229-40 |
| abstractText | Invariant natural killer T (iNKT) cells are a special subset of alphabeta T cells with invariant TCR, which recognize alpha-galactosylceramide (alpha-GalCer) presented by CD1d. In addition to signals through the invariant TCR upon stimulation with alpha-GalCer, costimulatory signals, such as signals through CD28 and OX40, are indispensable for full activation of iNKT cells. In this study, we investigated the functions of a well-known costimulatory molecule, glucocorticoid-induced TNF receptor (GITR), on Ag-induced iNKT cell activation. Unexpectedly, engagement of GITR by agonistic mAb DTA-1 suppressed proliferation and cytokine production of iNKT cells upon alpha-GalCer stimulation. In addition, GITR signals in iNKT cells during only the Ag-priming phase was sufficient to inhibit the iNKT cell activation. Consistent with these results, the GITR-deficient iNKT cells showed enhanced proliferation and increased cytokine production upon alpha-GalCer stimulation both in vitro and in vivo. Furthermore, the in vivo administration of alpha-GalCer suppressed tumor metastasis more efficiently in GITR-deficient mice than in wild-type mice. Collectively, GITR plays a co-inhibitory role in Ag-induced iNKT cell activation. |
