Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells Journal Article
| Authors: | Chen, S.; Ndhlovu, L. C.; Takahashi, T.; Takeda, K.; Ikarashi, Y.; Kikuchi, T.; Murata, K.; Pandolfi, P. P.; Riccardi, C.; Ono, M.; Sugamura, K.; Ishii, N. |
| Article Title: | Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells |
| Abstract: | Invariant natural killer T (iNKT) cells are a special subset of αβ T cells with invariant TCR, which recognize α-galactosylceramide (α-GalCer) presented by CD1d. In addition to signals through the invariant TCR upon stimulation with α-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 α-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 α-GalCer stimulation both in vitro and in vivo. Furthermore, the in vivo administration of a-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. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; protein function; lymphocyte proliferation; animal cell; mouse; animal; animals; mice; animal experiment; animal model; in vivo study; cytotoxicity; in vitro study; wild type; mice, inbred c57bl; physiology; immunoregulation; c57bl mouse; monoclonal antibody; cancer inhibition; cytokine; immunology; lymphocyte activation; glucocorticoid; natural killer cell; killer cells, natural; cytokine production; cytotoxicity, immunologic; tumor necrosis factor receptor; protein deficiency; immunostimulation; glucocorticoid induced tumor necrosis factor receptor; protein determination; t lymphocyte activation; glucocorticoid induced tumor necrosis factor receptor antibody; glucocorticoids; alpha galactosylceramide; cd1d antigen; natural killer t cell; receptors, tumor necrosis factor; galactosylceramide; cd1 antigen; antigens, cd1; co-inhibitory signal; glucocorticoid-induced tnf receptor; invariant nkt cell; alpha-galactosylceramide; galactosylceramides |
| Journal Title: | European Journal of Immunology |
| Volume: | 38 |
| Issue: | 8 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2008-08-01 |
| Start Page: | 2229 |
| End Page: | 2240 |
| Language: | English |
| DOI: | 10.1002/eji.200838167 |
| PUBMED: | 18624295 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "CODEN: EJIMA" - "Source: Scopus" |
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