title: Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus.
abstract: An immunoinhibitory receptor, lymphocyte activation gene-3 (LAG-3), which is mainly expressed in T-cells, is involved in the immune evasion of several pathogens causing chronic infections and tumors. However, unlike human or mouse LAG-3, no functional analysis of LAG-3 has been reported in domestic animals. Thus, in this study, bovine LAG-3 expression was analyzed in bovine leukemia virus (BLV)-infected cattle. In persistent lymphocytotic (PL) cattle, the numbers of LAG-3(+)CD4(+) cells and LAG-3(+)CD8(+) cells were conserved whilst the number of MHC class II(+) cells was remarkably higher than in the control animals. In contrast, the mean fluorescence intensity (MFI) for LAG-3 on PBMCs from PL cattle was significantly increased compared to control and asymptomatic (AL) cattle. Specifically, the LAG-3 expression level was significantly increased in both CD4(+) and CD8(+) T cells from PL cattle. LAG-3 expression correlated positively with increased numbers of lymphocytes and MHC class II(+) cells in infected animals. Preliminary results from PD-L1 and LAG-3 blockade assay revealed that IFN-γ and IL-2 expressions were significantly up-regulated by addition of anti- PD-L1 and LAG-3 antibodies in PBMCs from PL cattle. These findings suggest that LAG-3 might be involved in the inhibition of T-cell function through its binding and signaling on MHC class II molecule during BLV infection.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. konnai@vetmed.hokudai.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.forename: Saori
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shirai
authors.forename: Ryoyo
authors.initials: R
authors.lastname: Ikebuchi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Okagawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sunden
authors.forename: Claro N
authors.initials: CN
authors.lastname: Mingala
authors.forename: Misao
authors.initials: M
authors.lastname: Onuma
authors.forename: Shiro
authors.initials: S
authors.lastname: Murata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D060890:B7-H1 Antigen / Q000378:metabolism; D002417:Cattle; D016583:Enzootic Bovine Leukosis / Q000235:genetics* / Q000276:immunology*; D001909:Leukemia Virus, Bovine; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D008218:Lymphocytosis / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; D000093322:Lymphocyte Activation Gene 3 Protein