Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen presenting cell and T cell infiltration into allogeneic heart grafts

Eggenhofer, E. and Steinmann, J. F. and Renner, P. and Slowik, P. and Piso, P. and Geissler, E. K. and Schlitt, H. J. and Dahlke, M. H. and Popp, F. C. (2011) Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen presenting cell and T cell infiltration into allogeneic heart grafts. TRANSPLANT IMMUNOLOGY, 24 (3). pp. 157-163. ISSN 0966-3274, 2210-3384

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Abstract

Donor-derived mesenchymal stem cells (MSC) can induce long-term acceptance in a rat heart transplantation model when injected prior to transplantation in combination with mycophenolate mofetil (MMF). In contrast, MSC alone cause accelerated graft rejection. To better understand these conflicting data we studied the effects of MSC and MMF on lymphocyte populations in heart allografts and secondary lymphatic organs. Allogeneic MSC injected prior to transplantation are immunogenic in this model because activated CD4(+) and CD8(+) cells emerged earlier in secondary lymphatic organs of MSC- and MSC/MMF-treated animals, compared to animals not treated with MSC. Consequently T cells infiltrated the grafts of MSC-only treated animals promptly causing accelerated graft rejection. However, few T cells or antigen-presenting cells (APC) infiltrated the grafts of animals treated with MSC and MMF. Consistent with this finding, intercellular adhesion molecule 1 (ICAM-1) and E-selectin was down-regulated exclusively in MSC/MMF-treated grafts, indicating that MSC together with MMF interfere with endothelial activation. Additionally, the presence of interferon-gamma (IFN-gamma) enhanced MSC capabilities to suppress T cell proliferation in vitro. Interestingly, MMF did not influence serum IFN-gamma levels in vivo. Together, our data indicate that MSC pre-activate T cells, but co-treatment with MMF eliminates these T cells, decreases intragraft APC and T cell trafficking by inhibiting endothelial activation, and allows IFN-gamma stimulation of suppressive MSC. (C) 2010 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: MARROW STROMAL CELLS; INTERFERON-GAMMA; DENDRITIC CELLS; CARDIAC ALLOGRAFT; PROGENITOR CELLS; IN-VIVO; TRANSPLANTATION; REJECTION; RAPAMYCIN; ACTIVATION; Mesenchymal stem cell; Solid organ transplantation; Mycophenolate mofetil; Antigen; Presenting cells; T cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Jun 2020 07:18
Last Modified: 22 Jun 2020 07:18
URI: https://pred.uni-regensburg.de/id/eprint/20957

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