Abstract :Amniotic fluid-derived stem cells (AFSCs) might be an alternative and less-invasive source of mesenchymal stem cells (MSCs) that could be used in regenerative medicine. AFSCs share the similar immunosuppressive properties with MSCs derived from bone marrow. However, the mechanisms behind the immune responses of AFSCs remain unclear. In this paper, we investigated inhibitory effect of AFSCs on immune cells proliferation induced by mitogen. Measurement of IFN-γ levels in the culture supernatants revealed a significant decrease of the cytokine when mitogen-activated peripheral blood mononuclear cells (PBMCs) were cultured in the presence of AFSCs. AFSCs constitutively expressing HLA-ABC and CD274 increased the expression levels of them with the treatment of IFN-γ. Whereas, HLA-DR, HLA-G and co-stimulatory molecules such as CD80, CD86 were not expressed. Moreover, IFN-γ treatment also induced the expressions of indoleamine 2,3-dioxygenase (IDO), transforming growth factor-β (TGF-β) and IL-10 in AFSCs. Treatment with IDO inhibitor and anti-CD274 reverted the modulatory effect of the AFSCs. From these data, we suggest that AFSCs carry the immunomodulatory characteristics mediated by CD274 and IDO. Findings obtained from this study could be utilized for the development of amniotic fluid-derived stem cell therapy products with the further study.