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Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10
Experimental & Molecular Medicine ; : 315-324, 2009.
Article in English | WPRIM | ID: wpr-136591
ABSTRACT
Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naive or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naive and pre-activated T cells in which IL-10 and IDO play important roles.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Tryptophan / Lymphocyte Activation / T-Lymphocytes / Cells, Cultured / Lymphokines / Interleukin-10 / Cell Proliferation / Indoleamine-Pyrrole 2,3,-Dioxygenase / Receptors, Interleukin-10 / Mesenchymal Stem Cells Limits: Animals Language: English Journal: Experimental & Molecular Medicine Year: 2009 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Tryptophan / Lymphocyte Activation / T-Lymphocytes / Cells, Cultured / Lymphokines / Interleukin-10 / Cell Proliferation / Indoleamine-Pyrrole 2,3,-Dioxygenase / Receptors, Interleukin-10 / Mesenchymal Stem Cells Limits: Animals Language: English Journal: Experimental & Molecular Medicine Year: 2009 Type: Article