Galectin-9 increases Tim-3+ dendritic cells and CD8+ T cells and enhances antitumor immunity via galectin-9-Tim-3 interactions.
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.
Nagahara
Keiko
K
Department of Immunology and Immunopathology, Kagawa University, Kita-gun, Kagawa, Japan.
Arikawa
Tomohiro
T
Oomizu
Souichi
S
Kontani
Keiichi
K
Nobumoto
Atsuya
A
Tateno
Hiroaki
H
Watanabe
Kota
K
Niki
Toshiro
T
Katoh
Shigeki
S
Miyake
Minoru
M
Nagahata
Syun-Ichiro
S
Hirabayashi
Jun
J
Kuchroo
Vijay K
VK
Yamauchi
Akira
A
Hirashima
Mitsuomi
M
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*
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