Development of donor-specific chimerism and tolerance in composite tissue allografts under alphabeta-T-cell receptor monoclonal antibody and cyclosporine a treatment protocols.
Recently, we induced donor-specific tolerance to rat hindlimb allografts under a 35-day course of alphabeta-T-cell receptor monoclonal antibody (alphabeta-TCR mAb) and cyclosporine A (CsA). In this report, we investigated the role of shorter alphabeta-TCR/CsA protocols on tolerance induction. We performed 52 hindlimb transplantations, between Lewis-Brown-Norway (LBN, F1) donors and Lewis recipients to test the impact of 21-, 7-, and 5-day protocols of combined alphabeta-TCR/CsA treatment on tolerance induction. Donor-specific tolerance and immunocompetence were tested by mixed lymphocyte reaction (MLR) in vitro and by standard skin grafting in vivo. The efficacy of immunosuppressive protocol and donor-specific chimerism was assessed by flow cytometry. All transplants under 5, 7, and 21 days of combined alphabeta-TCR/CsA therapy survived over 350 days. Clinical tolerance and immunocompetence were confirmed by skin grafting in vivo and MLR in vitro. Flow cytometry revealed a high level of donor chimerism in the peripheral blood of long-term survivors. The extension of survival of limb allografts and allo-unresponsiveness were directly associated with the development of stable chimerism in the tolerant recipients.
Ozer
Kagan
K
Department of Plastic Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Izycki
Dariusz
D
Zielinski
Maciej
M
Siemionow
Maria
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D008297:Male; D011336:Probability; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D016378:Tissue Transplantation / Q000379:methods; D018183:Transplantation Chimera / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D016572:Cyclosporine