Possible involvement of soluble B7-H4 in T cell-mediated inflammatory immune responses.
B7-H4, a newly identified B7 family molecule, is reported to regulate T cell activation. However, the expression and function of B7-H4 remain controversial. Here, we demonstrated that B7-H4 expression in immune cells was undetectable at both the transcription and cell-surface protein levels. B7-H4 transfectants augmented anti-CD3 mAb-induced re-directed cytotoxicity and this was inhibited by anti-B7-H4 mAb. In a hapten-induced contact hypersensitivity model, treatment with anti-B7-H4 mAb at sensitization, but not at challenge, efficiently suppressed the ear swelling and CD8(+) T cell activation assessed by CD25 expression and IFN-gamma production. We found that cells expressing B7-H4 secreted soluble B7-H4 and the serum B7-H4 level increased with disease progression in lupus-prone and collagen-induced arthritis autoimmune mice and after the antigen challenge in allergic inflammatory diseases. Our results suggest a different action of B7-H4 in T cell-mediated inflammatory responses and the possible involvement of soluble B7-H4 in inflammatory immune responses.
Kamimura
Yosuke
Y
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Kobori
Hiroko
H
Piao
Jinhua
J
Hashiguchi
Masaaki
M
Matsumoto
Koichiro
K
Hirose
Sachiko
S
Azuma
Miyuki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D017252:CD3 Complex; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475824:Vtcn1 protein, mouse