title: Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro.
abstract: Programmed death-1 (PD-1) is a known immunoinhibitory receptor that contributes to immune evasion of various tumor cells and pathogens causing chronic infection, such as bovine leukemia virus (BLV) infection. First, in this study, to establish a method for the expression and functional analysis of bovine PD-1, hybridomas producing monoclonal antibodies (mAb) specific for bovine PD-1 were established. Treatment with these anti-PD-1 mAb enhanced interferon-gamma (IFN-γ) production of bovine peripheral blood mononuclear cells (PBMC). Next, to examine whether PD-1 blockade by anti-PD-1 mAb could upregulate the immune reaction during chronic infection, the expression and functional analysis of PD-1 in PBMC isolated from BLV-infected cattle with or without lymphoma were performed using anti-PD-1 mAb. The frequencies of both PD-1+ CD4+ T cells in blood and lymph node and PD-1+ CD8+ T cells in lymph node were higher in BLV-infected cattle with lymphoma than those without lymphoma or control uninfected cattle. PD-1 blockade enhanced IFN-γ production and proliferation and reduced BLV-gp51 expression and B-cell activation in PBMC from BLV-infected cattle in response to BLV-gp51 peptide mixture. These data show that anti-bovine PD-1 mAb could provide a new therapy to control BLV infection via upregulation of immune response.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. okazu@vetmed.hokudai.ac.jp.
authors.forename: Ryoyo
authors.initials: R
authors.lastname: Ikebuchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Okagawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Chie
authors.initials: C
authors.lastname: Nakajima
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shiro
authors.initials: S
authors.lastname: Murata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D002417:Cattle; D003412:Cricetulus; D016583:Enzootic Bovine Leukosis / Q000276:immunology* / Q000821:virology; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D001909:Leukemia Virus, Bovine / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma