PGE2 contributes to in vitro MSC-mediated inhibition of non-specific and antigen-specific T cell proliferation in MS patients.
Current theories of multiple sclerosis (MS) induction and progression place autoreactive T cells in the focus of the pathogenesis. Mesenchymal/stromal stem cells (MSC) have become a promising alternative approach for pathogenic therapy of MS due to their immunomodulatory properties, underlying mechanisms of which are intensive study. The objective of the research was to investigate the contribution of PGE2 to MSC-mediated suppression in patients with MS using in vitro model of mitogen- and myelin-stimulated T cell cocultivation with autologous/allogeneic MSC. We have showed that PGE2 production depends on cell-to-cell contact of MSC and lymphocytes. The antigenic stimulation did not affect PGE2 production following cocultivation of MSC and PBMC, and it is the presence of MSC in cell culture that significantly increases PGE2 production irrespective of antigenic cultivation conditions. Simultaneously, PGE2 synthesis correlated with indexes of MSC-mediated suppression of mitogen- and myelin-stimulated T cell proliferation in patients with MS. No significant differences in PGE2 production by autologous and allogeneic MSC have been established. These results have demonstrated that in patients with MS, PGE2 is one of the possible factors of MSC immunosuppression. The interrelation between PGE2 concentrations and T cell proliferation suppression mediated by MSC may explain one of the immune mechanisms of cell therapy, which is crucial for the further proper use of MSC in MS research and pathogenic treatment.
Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus.
M
M
Zafranskaya
D
D
Nizheharodava
M
M
Yurkevich
G
G
Ivanchik
Y
Y
Demidchik
H
H
Kozhukh
A
A
Fedulov
D000328:Adult; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008934:Mitogens; D009103:Multiple Sclerosis / Q000276:immunology*; D010835:Phytohemagglutinins; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
D008934:Mitogens; D010835:Phytohemagglutinins; D015232:Dinoprostone