2024-03-29T15:10:25Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/826662023-01-20T02:25:24Zhdl_2115_20048hdl_2115_140Programmed death-ligand 1 expression in swine chronic infections and enhancement of interleukin-2 production via programmed death-1/programmed death-ligand 1 blockadeGanbaatar, OtgontuyaKonnai, SatoruOkagawa, TomohiroNojima, YutaroMaekawa, NaoyaIchikawa, YoshikiKobayashi, AtsushiShibahara, TomoyukiYanagawa, YojiroHiguchi, HidetoshiKato, YukinariSuzuki, YasuhikoMurata, ShiroOhashi, Kazuhikointerleukin-2PD-1PD-L1swine diseases649Introduction: Chronic infections lead to the functional exhaustion of T cells. Exhausted T cells are phenotypically differentiated by the surface expression of the immunoinhibitory receptor, such as programmed death-1 (PD-1). The inhibitory signal is produced by the interaction between PD-i and its PD-ligand 1 (PD-L1) and impairs the effector functions of T cells. However, the expression dynamics of PD-L1 and the immunological functions of the PD-1/ PD-Ll pathway in chronic diseases of pigs are still poorly understood. In this study, we first analyzed the expression of PD-L1 in various chronic infections in pigs, and then evaluated the immune activation by the blocking assay targeting the swine PD-1/PD-L1 pathway. Methods: In the initial experiments, anti-bovine PD-L1 monoclonal anti-bodies (mAbs) were tested for cross-reactivity with swine PD-L1. Subsequently, immunohistochemical analysis was conducted using the anti-PD-L1 mAb. Finally, we assessed the immune activation of swine peripheral blood mononuclear cells (PBMCs) by the blockade with anti-PD-L1 mAb. Results: Several anti-PD-L1 mAbs tested recognized swine PD-Ll-expressing cells. The binding of swine PD-Ll protein to swine PD-1 was inhibited by some of these cross-reactive mAbs. In addition, immunohistochemical analysis revealed that PD-L1 was expressed at the site of infection in chronic infections of pigs. The PD-L1 blockade increased the production of interleukin-2 from swine PBMCs. Conclusions: These findings suggest that the PD-1/PD-L1 pathway could be also involved in immunosuppression in chronic infections in pigs. This study provides a new perspective on therapeutic strategies for chronic diseases in pigs by targeting immunosuppressive pathways.John Wiley & SonsJournal Articlehttp://hdl.handle.net/2115/826662050-4527Immunity, inflammation and disease94157315832021-08-20enginfo:doi/10.1002/iid3.510none