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Chronic graft-versus-host disease (cGVHD) is a complication after minor antigen mismatched bone marrow transplantation (BMT) characterized by an autoimmune-type reaction in various organs. Aberration in T cell regulation is involved, with donor mesenchymal stem cells (MSCs) playing a possible role in immunomodulation. In a minor-antigen mismatched mouse BMT model, transplantation of mismatched, but not syngeneic MSCs triggered the onset of cGVHD, and was associated with fibrosis, increased IL-6 secretion, decreased Foxp3+ regulatory T cells and increased Th17 in the peripheral blood. Mismatched MSCs alone were sufficient to induce cGVHD, while removal of donor MSCs rescued mice from cGVHD. RAG2 knockout recipient mice did not suffer cGVHD, indicating that host T cells were involved. Residual host-derived T cells were significantly higher in cGVHD patients compared to non-cGVHD patients. In conclusion, donor MSCs react with residual host T cells to trigger the progression of cGVHD.

Donor mesenchymal stem cells trigger chronic graft-versus-host disease following minor antigen-mismatched bone marrow transplantation