Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications

Figure 1

Immunoregulatory effect of MSCs on T lymphocytes. MSCs can induce the sustained expression of CTLA-4 and CD69 activation molecules on T cells, which have been related with generation of cells with immunoregulatory properties. Cell-to-cell contact seems to be required for the increase of CTLA-4 expression. Dependent and independent mechanisms of cellular contact are involved in the decrease of proliferation of CD4⁺ and CD8⁺ T cells and in generation of Foxp3⁺ Tregs by MSCs. Cytokines such as IL-10 can stimulate the expression and secretion of HLA-G5 by MSCs and in turn it stimulates the secretion of IL-10 in a positive feedback loop. The initial contact between MSCs and T lymphocytes seems to be required for initiation of the feedback loop. PGE₂ secreted by MSCs is involved in generation of Tr1 cells. HLA-G5 supports differentiation of Th2 cells and IDO decrease differentiation of Th17.