An alternative conditioning regimen for induction of specific skin graft tolerance across full major histocompatibility complex barriers.
Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose total body irradiation (TBI; 3-6 Gy) and allogeneic bone marrow cells. An alternative cytoreductive strategy that is well-recognized in bone marrow transplantation, but has not been evaluated extensively in organ allograft recipients, involves the use of a combined chemotherapeutic drug treatment. The present data show that conditioning with low dose TBI, in a MHC-disparate donor-recipient combination, can be successfully substituted by a combined single low-dose dimethyl myleran (DMM)/cyclophosphamide (CY) therapy, resulting in both stable, mixed chimerism and specific skin graft tolerance.
de Vries-van der Zwan
A
A
Department of Transplantation Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
van der Pol
M A
MA
de Waal
L P
LP
Boog
C J
CJ
D000818:Animals; D002066:Busulfan / Q000031:analogs & derivatives / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D017741:Survivors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D006183:H-2 Antigens; D007166:Immunosuppressive Agents; C002037:dimethylmyleran; D003520:Cyclophosphamide; D002066:Busulfan