Overexpression of programmed death ligands in naturally occurring postweaning multisystemic wasting syndrome

Postweaning multisystemic wasting syndrome (PMWS) is regarded as an immunosuppressive disease in pigs caused by porcine circovirus type 2 (PCV2). Immune inhibitory receptors, particularly programmed death 1/programmed death-ligands (PD-1/PD-Ls) are presumably involved in the immunopathogenesis of PMWS. The aim of this investigation was to examine the relationship of immune inhibitory receptors and immunocompromised by PMWS. Nine 45-day-old conventional pigs were selected from a farm where pigs exhibited typical signs of PMWS (wasting and respiratory disorders) and tested positive for PCV2 infection by polymerase chain reaction (PCR). Six pigs were selected as controls due to their notably healthy state and absence of PCV2 infection. Heparinized blood samples were taken from each pig for pathogen detection and isolation of peripheral blood mononuclear cells (PBMCs), from which mRNA expression of immunomodulatory molecule (PD-1, PD-L1, PD-L2, PTEN, CTLA-4, LAG-3, and Foxp3) and cytokines (IL-10, IL-2, and IFN-γ) was determined. Proliferation of PBMCs was also assessed by flow cytometry utilizing cellular labeling dilutions for detection. The mRNA levels of PD-L1 (p<0.01), PD-L2 (p<0.05), and PTEN (p<0.01) were remarkably increased in the PBMCs of diseased pigs compared to healthy pigs, whereas no change was observed for PD-1, CTLA-4, LAG-3, and Foxp3 expression. Cytokine IL-10 mRNA levels were significantly elevated (p<0.01), while IL-2 and IFN-γ mRNA levels tended to be only slightly increased in the PBMCs of affected pigs compared to healthy controls. The proliferation of PBMCs was also decreased in diseased pigs. These data suggest that overexpression of PD-L1 and PD-L2 mRNA is one mechanism by which immunosupression of PMWS pigs occurs, supporting a new therapeutic strategy focused on PD-Ls for pigs suffering from PMWS.