A Significant Role of Mesehchymal Stem Cells in Immune Processes and Pathogenic Fibrosis In Ocular Chronic Graft Versus Host Disease

Abstract

Purpose: : Chronic graft-versus-host disease (cGVHD) is a complication after minor antigen mismatched bone marrow transplantation (BMT) that involves the eyes and other mucous membranes. Aberration in T cell regulation is involved, with mesenchymal stem cells (MSCs) playing a possible role in immunomodulation.

Methods: : After isolating MSCs (PDGFRα⁺, Sca-1⁺ cells) by flowcytometry, we examined the effects of transplanting mismatched MSCs or removing MSCs from donor cells prior to mismatched BMT. We also measured tear volume after transplation. In addition, the expression level of IL-6 in the supernatants of co-cultures between MSCs and T cells, the ratio of Foxp3⁺ T cells/CD4⁺ T cells and Th 17 T cells/CD4⁺ T cells in the peripheral blood or spleen cells were analysed.

Results: : We found that donor MSC depletion suppressed fibrotic lesions associated with cGVHD in various organs and preserved lacrimal gland function. When nude mice were used as recipients, cGVHD was mild despite mismatched MSCs, suggesting that interaction with host T cells were involved. Transplantation of mismatched, but not syngeneic MSCs was associated with increased IL-6 in the supernatants of co-cultures between MSCs and T cells, decreased Foxp3⁺ regulatory T cells and increased Th 17 T cells in the peripheral blood or spleen cells.

Conclusions: : We conclude that donor MSCs react with residual host T cells to trigger an autoimmune-type response in the progression of ocular cGVHD.

Keywords: cornea: tears/tear film/dry eye • immunomodulation/immunoregulation • transplantation