Involvement of GITRL-GITR costimulatory pathway in T cell-mediated immune responses in vivo (88.23)
| Autor: | Jinhua Piao, Kamimura Yosuke, Igarashi Hanna, Hideyuki Iwai, Hashiguchi Massaaki, Sakaguchi Shimon, Miyuki Azuma |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 178:S143-S143 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.178.supp.88.23 |
| Popis: | GITR is expressed on CD25+ regulatory T cells at high levels. GITR is also expressed on conventional CD4 and CD8 T cells and acts as a potent costimulatory molecule based on the studies using agonistic anti-GITR mAb. The physiological impact of GITR-mediated signal that is delivered by GITRL is still unknown. Here, we report the effects of neutralizing anti-GITRL mAb (MIH44) treatment in tumor and hapten-induced contact hypersensitivity (CH) models. Inoculation of GITRL-transduced tumor cells (GITRL-P815 and GITRL-SCCVII) into the syngeneic mice efficiently inhibited their tumor growth, suggesting the enhanced antitumor immune responses by tumor-associated GITRL. Administration of anti-GITRL mAb reversed the GITRL-induced antitumor responses, but these effects were decreased in the anti-CD25 mAb treated mice. Treatment with anti-GITRL mAb did not affect the tumor growth of parental tumors. In a CH model, the anti-GITRL mAb treatment at the sensitization, but not at the challenge, efficiently suppressed ear swelling. This inhibitory effect was long-lasting. The anti-GITRL mAb treatment significantly decreased the percentages of IFN-γ+CD8+ and CD25+ T cells. These inhibitory effects by anti-GITRL treatment were reduced in the anti-CD25 pre-treated mice. Our data suggest that GITR-GITRL costimulatory pathway is involved certainly in activation of conventional T cells and regulatory T cells may affect the GITRL-costimulatory pathway. |
| Databáze: | OpenAIRE |
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