Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD.
Co-stimulatory molecules expressed on T cells critically regulate donor T-cell activation and are implicated in acute GVHD after allogeneic BMT. We here investigated the role of interaction between B7-related protein-1 (B7RP-1) and ICOS in murine acute GVHD model that received T cell-depleted BM cells and splenocytes. Administration of blocking anti-B7RP-1 mAb significantly reduced the lethality and symptoms in acute GVHD. A significant hypo-responsiveness of splenocytes to host alloantigen was observed in the recipient mice treated with anti-B7RP-1 mAb. Moreover, acute GVHD was significantly reduced in the recipients of T cells composed of ICOS-deficient CD8 T cells and WT CD4 T cells compared with that in the recipients of T cells composed of WT CD8 T cells and ICOS-deficient CD4 T cells. These results suggested that B7RP-1/ICOS co-stimulatory signal plays a role in the activation of alloantigen-reactive donor T cells, particularly in CD8 T cells, in murine acute GVHD model, and that the blockade of B7RP-1/ICOS interaction may be useful for selectively manipulating allo-reactive T cells in the recipients with acute GVHD.
Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan. junya-f@juntendo.ac.jp
Junya
J
Fujimura
Kazuyoshi
K
Takeda
Yuki
Y
Kaduka
Masahoro
M
Saito
Hisaya
H
Akiba
Hideo
H
Yagita
Yuichiro
Y
Yamashiro
Toshiaki
T
Shimizu
Ko
K
Okumura
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000097:blood; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D018709:Statistics, Nonparametric; D015534:Trans-Activators / Q000378:metabolism; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007519:Isoantigens; D015534:Trans-Activators; D007371:Interferon-gamma