TGF-β2 decreases surface expression of MHC I and MHC II on equine bone marrow-derived mesenchymal stromal cells.

Abstract

Abstract Allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) are a promising cell source for treatment of inflammatory diseases, but elicit immune responses in vivo due to recipient recognition of mismatched Major Histocompatibility Complex (MHC) molecules. The purposes of this study were to evaluate the effectiveness of TGF-β2 in decreasing and stabilizing MHC expression on equine bone marrow-derived MSCs before and after IFN-γ stimulation. FACS analysis showed that MSCs treated with 1, 5, or 10 ng/ml of TGF-β2 had significantly reduced MHC I expression. MHC I expression levels on TGF-β2-treated MSCs were also quantified and determined to be similar to fetal fibroblasts. MHC II expression in two positive animals was greatly reduced compared to untreated MSCs. MSCs pre-treated and continuously treated with 1 ng/ml TGF-β2 had significantly lower MHC I expression following stimulation with IFN-γ for 72 hours compared with untreated. Continuously treated MSCs that were baseline positive for MHC II had significantly lower MHC II expression following IFN-γ stimulation, but there was no significant difference in MHC II expression between TGF-β2-treated and untreated MHC II-negative MSCs after IFN-γ stimulation. These results indicate TGF-β2 treatment has significant promise for reducing recipient immune recognition of MHC-mismatched molecules on allogeneic MSCs, but further work is needed to maintain MHC expression stability.