Strategies to develop chimerism in vascularized skin allografts across MHC barrier.
In this study, we investigated the effects of 7-day-protocols of alphabeta-T-cell receptor monoclonal antibody (alphabeta-TCRmAb), cyclosporine A (CsA), and tacrolimus (FK-506) immunosuppressive monotherapies, and their combinations on the survival of vascularized skin allografts (VSA). Forty-two transplantations of VSA across a strong MHC barrier were performed between ACI (RT1a) donors and Lewis (RT1(l)) recipients in seven groups. Isograft and allograft rejection controls received no treatment. Treatment groups received a 7-day protocol of alphabeta-TCRmAb, CsA, or FK-506 monotherapy, or a combination of alphabeta-TCRmAb/CsA and alphabeta-TCRmAb/FK-506. VSA transplants were evaluated on a daily basis. Donor-specific chimerism was determined by flow cytometry (FC). The combined protocols of alphabeta-TCRmAb/FK-506 and alphabeta-TCRmAb/CsA significantly prolonged VSA survivals compared to monotherapy groups ( P < 0.005). FC analysis revealed 15.82% of donor-specific chimerism on day 7 under the alphabeta-TCRmAb/CsA protocol and a gradual chimerism decline on day 63 posttransplant. The significant extension of VSA survival achieved under 7-day protocols of combined therapies was directly associated with the presence of donor-specific chimerism.
Demir
Yavuz
Y
Department of Plastic Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Ozmen
Selahattin
S
Klimczak
Aleksandra
A
Mukherjee
Abir Lal
AL
Siemionow
Maria Z
MZ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D046528:Chimerism / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013524:Surgical Flaps / Q000098:blood supply* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine; D016559:Tacrolimus