title: Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus.
abstract: BACKGROUND
  An immunoinhibitory receptor, programmed death-1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), are involved in immune evasion mechanisms for several pathogens causing chronic infections and for neoplastic diseases. However, little has been reported for the functions of these molecules in chickens. Thus, in this study, their expressions and roles were analyzed in chickens infected with Marek's disease virus (MDV), which induces immunosuppression in infected chickens.
  
  
  RESULTS
  A chicken T cell line, Lee1, which constitutively produces IFN-γ was co-cultured with DF-1 cells, which is a spontaneously immortalized chicken fibroblast cell line, transiently expressing PD-L1, and the IFN-γ expression level was analyzed in the cell line by real-time RT-PCR. The IFN-γ expression was significantly decreased in Lee1 cells co-cultured with DF-1 cells expressing PD-L1. The expression level of PD-1 was increased in chickens at the early cytolytic phase of the MDV infection, while the PD-L1 expression level was increased at the latent phase. In addition, the expression levels of PD-1 and PD-L1 were increased at tumor lesions found in MDV-challenged chickens. The expressions levels of PD-1 and PD-L1 were also increased in the spleens and tumors derived from MDV-infected chickens in the field.
  
  
  CONCLUSIONS
  We demonstrated that the chicken PD-1/PD-L1 pathway has immunoinhibitory functions, and PD-1 may be involved in MD pathogenesis at the early cytolytic phase of the MDV infection, whereas PD-L1 could contribute to the establishment and maintenance of MDV latency. We also observed the increased expressions of PD-1 and PD-L1 in tumors from MDV-infected chickens, suggesting that tumor cells transformed by MDV highly express PD-1 and PD-L1 and thereby could evade from immune responses of the host.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Matsuyama-Kato
authors.forename: Shiro
authors.initials: S
authors.lastname: Murata
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Isezaki
authors.forename: Rika
authors.initials: R
authors.lastname: Kano
authors.forename: Sara
authors.initials: S
authors.lastname: Takasaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology*; D002460:Cell Line; D002645:Chickens; D018920:Coculture Techniques; D005347:Fibroblasts / Q000821:virology; D020869:Gene Expression Profiling; D057131:Immune Evasion; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D025922:Mardivirus / Q000276:immunology* / Q000472:pathogenicity*; D008380:Marek Disease / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma