Reciprocal Interactions Between Human Mesenchymal Stem Cells and γδ T Cells Or Invariant Natural Killer T Cells

Abstract

Abstract The immunomodulatory activities of human mesenchymal stem cells (MSCs) provide a rational basis for their application in the treatment of immune-mediated diseases, such as graft versus host disease and multiple sclerosis. The effects of MSCs on invariant natural killer T (iNKT) and γδ T cells, both involved in the pathogenesis of autoimmune diseases, are unknown. Here, we investigated the effects of MSCs on in vitro expansion of these unconventional T-cell populations. MSCs inhibited iNKT (Vα24+Vβ11+) and γδ T (Vδ2+) cell expansion from peripheral blood mononuclear cells in both cell-to-cell contact and transwell systems. Such inhibition was partially counteracted by indomethacin, a prostaglandin E2 inhibitor. Block of indoleamine 2,3-deoxygenase and transforming growth factor β1 did not affect Vα24+Vβ11+ and Vδ2+ cell expansion. MSCs inhibited interferon-γ production by activated Vα24+Vβ11+ and impaired CD3-mediated proliferation of activated Vα24+Vβ11+ and Vδ2+ T cells, without affecting their cytotoxic potential. MSCs did not inhibit antigen processing/presentation by activated Vδ2+ T cells to CD4+ T cells. In contrast, MSCs were lysed by activated Vδ2+ T cells through a T-cell receptor-dependent mechanism. These results are translationally relevant in view of the increasing interest in MSC-based therapy of autoimmune diseases.