B7-H1 (CD274) inhibits the development of herpetic stromal keratitis (HSK).
The co-signaling molecule B7-H1 (CD274) functions as both a co-inhibitor through programmed death-1 (PD-1) receptor and a co-stimulator via an as-yet-unidentified receptor on T cells. We investigated the physiological role of endogenous B7-H1 in the pathogenesis of herpetic stromal keratitis (HSK) caused by herpes simplex virus type 1 (HSV-1). Following HSV-1 infection of the cornea of mice, B7-H1 expression was up-regulated in the CD11b+ macrophage population in the draining lymph nodes (dLN) and in the inflamed cornea. In addition, HSV-1 infection significantly increased PD-1 expression on CD4+ T cells in the dLN and inflamed cornea. The administration of antagonistic B7-H1 monoclonal antibody resulted in the proliferation of HSV-specific CD4+ T cells that secreted interferon (INF)-gamma, and inhibited the apoptosis of HSV-specific CD4+ T cells, which exaggerated HSK. These results strongly suggest that the B7-H1 may be involved in suppression of the development of HSK.
Jun
Her
H
Department of Ophthalmology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Seo
Su K
SK
Jeong
Hye-Young
HY
Seo
Hyoun-Mi
HM
Zhu
Gefeng
G
Chen
Lieping
L
Choi
In-Hak
IH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003315:Cornea / Q000276:immunology / Q000473:pathology; D018259:Herpesvirus 1, Human; D007371:Interferon-gamma / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000037:antagonists & inhibitors / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000821:virology; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D039481:CD11b Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D007371:Interferon-gamma