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

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 gamma delta 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 (V alpha 24(+)V beta 11(+)) and gamma delta T (V delta 2(+)) 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 beta 1 did not affect V alpha 24(+)V beta 11(+) and V delta 2(+) cell expansion. MSCs inhibited interferon-gamma production by activated V alpha 24(+)V beta 11(+) and impaired CD3-mediated proliferation of activated V alpha 24(+)V beta 11(+) and V delta 2(+) T cells, without affecting their cytotoxic potential. MSCs did not inhibit antigen processing/presentation by activated V delta 2(+) T cells to CD4(+) T cells. In contrast, MSCs were lysed by activated V delta 2(+) 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. STEM CELLS 2009; 27: 693-702