title: Interleukin (IL)-10 induced by CD11b(+) cells and IL-10-activated regulatory T cells play a role in immune modulation of mesenchymal stem cells in rat islet allografts.
abstract: Mesenchymal stem cells (MSCs) are suggested to be immune modulators because of their therapeutic potential in transplantation. In the present study, we evaluated the therapeutic potential of autologous MSCs for preventing graft rejection after allogeneic rat islet transplantation. We assessed the ability of MSCs to elicit an antiproliferative response in alloreactive lymphocytes and tested the immunosuppressive effect of MSCs in allogeneic islet transplantation. In islet allotransplantation, injection of autologous MSCs or a subtherapeutic dose of cyclosporine A (CsA; 5 mg/kg) alone did not prolong allograft survival. However, graft survival was attained for >100 d in 33% of autologous MSC-plus-CsA-treated recipients, indicating that graft acceptance was achieved in a subgroup of allograft recipients. Splenocytes from autologous MSC-plus-CsA-treated rats exhibited a reduced mixed lymphocyte reaction (MLR)-proliferative response to donor stimulators and increased interleukin (IL)-10 release. Interestingly, after excluding host CD11b(+) cells, splenic T cells from autologous MSC-plus-CsA-treated rats did not produce IL-10 or did not inhibit proliferative responses under the same conditions. The use of autologous MSC-plus-CsA downregulated immune responses, inducing donor-specific T-cell hyporesponsiveness by reducing the production of proinflammatory cytokines and inducing antiinflammatory cytokine production, especially that of IL-10, during the early posttransplantation period. T-regulatory cells made a contribution at a later phase. In conclusion, the combined use of autologous MSCs and low-dose CsA exerted a synergistic immunosuppressive effect in an islet allograft model, suggesting a role for autologous MSCs as an immune modulator.
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Korea.
authors.forename: Yang-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Yu-Mee
authors.initials: YM
authors.lastname: Wee
authors.forename: Monica-Y
authors.initials: MY
authors.lastname: Choi
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Lim
authors.forename: Song-Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Duck-Jong
authors.initials: DJ
authors.lastname: Han
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000494:pharmacology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D039481:CD11b Antigen; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D016572:Cyclosporine