Reciprocal interactions between human mesenchymal stem cells and gammadelta 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 gammadelta 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 (Valpha24(+)Vbeta11(+)) and gammadelta T (Vdelta2(+)) 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 E(2) inhibitor. Block of indoleamine 2,3-deoxygenase and transforming growth factor beta1 did not affect Valpha24(+)Vbeta11(+) and Vdelta2(+) cell expansion. MSCs inhibited interferon-gamma production by activated Valpha24(+)Vbeta11(+) and impaired CD3-mediated proliferation of activated Valpha24(+)Vbeta11(+) and Vdelta2(+) T cells, without affecting their cytotoxic potential. MSCs did not inhibit antigen processing/presentation by activated Vdelta2(+) T cells to CD4(+) T cells. In contrast, MSCs were lysed by activated Vdelta2(+) 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.
Prigione
Ignazia
I
Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy. ignaziaprigione@ospedale-gaslini.ge.it
Benvenuto
Federica
F
Bocca
Paola
P
Battistini
Luca
L
Uccelli
Antonio
A
Pistoia
Vito
V
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000276:immunology*; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011458:Prostaglandins E; D007371:Interferon-gamma; D007213:Indomethacin