title: Galectin-9 increases Tim-3+ dendritic cells and CD8+ T cells and enhances antitumor immunity via galectin-9-Tim-3 interactions.
abstract: 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-gamma-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-gamma producing cells and IFN-gamma production. Depletion of Tim-3(+) DCs from DCs of Gal-9-treated tumor-bearing mice decreased the number of IFN-gamma-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.
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagahara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arikawa
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kontani
authors.forename: Atsuya
authors.initials: A
authors.lastname: Nobumoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tateno
authors.forename: Kota
authors.initials: K
authors.lastname: Watanabe
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Katoh
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyake
authors.forename: Syun-Ichiro
authors.initials: S
authors.lastname: Nagahata
authors.forename: Jun
authors.initials: J
authors.lastname: Hirabayashi
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D037161:Galectins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D053804:Granzymes / Q000235:genetics / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D007111:Immunity, Cellular / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D054353:Perforin / Q000235:genetics / Q000276:immunology; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; C508186:galectin 9, mouse; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes