Galectin-9 Increases Tim-3+ Dendritic Cells and CD8+ T Cells and Enhances Antitumor Immunity via Galectin-9-Tim-3 Interactions
2008; American Association of Immunologists; Volume: 181; Issue: 11 Linguagem: Inglês
10.4049/jimmunol.181.11.7660
ISSN1550-6606
AutoresKeiko Nagahara, Tomohiro Arikawa, Souichi Oomizu, Keiichi Kontani, Atsuya Nobumoto, Hiroaki Tateno, Kota Watanabe, Toshiro Niki, Shigeki Katoh, Minoru Miyake, Syun-Ichiro Nagahata, Jun Hirabayashi, Vijay K. Kuchroo, Akira Yamauchi, Mitsuomi Hirashima,
Tópico(s)Toxin Mechanisms and Immunotoxins
ResumoAbstract A Tim-3 ligand, galectin-9 (Gal-9), modulates various functions of innate and adaptive immune responses. In this study, we demonstrate that Gal-9 prolongs the survival of Meth-A tumor-bearing mice in a dose- and time-dependent manner. Although Gal-9 did not prolong the survival of tumor-bearing nude mice, transfer of naive spleen cells restored a prolonged Gal-9-induced survival in nude mice, indicating possible involvement of T cell-mediated immune responses in Gal-9-mediated antitumor activity. Gal-9 administration increased the number of IFN-γ-producing Tim-3+ CD8+ T cells with enhanced granzyme B and perforin expression, although it induced CD4+ T cell apoptosis. It simultaneously increased the number of Tim-3+CD86+ mature dendritic cells (DCs) in vivo and in vitro. Coculture of CD8+ T cells with DCs from Gal-9-treated mice increased the number of IFN-γ producing cells and IFN-γ production. Depletion of Tim-3+ DCs from DCs of Gal-9-treated tumor-bearing mice decreased the number of IFN-γ-producing CD8+ T cells. Such DC activity was significantly abrogated by Tim-3-Ig, suggesting that Gal-9 potentiates CD8+ T cell-mediated antitumor immunity via Gal-9-Tim-3 interactions between DCs and CD8+ T cells.
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