Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen
The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia.
- Research Organization:
- National Cancer Institute, Bethesda, MD (USA)
- OSTI ID:
- 6350710
- Journal Information:
- J. Exp. Med.; (United States), Vol. 169:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BONE MARROW
TRANSPLANTS
IMMUNITY
RADIOINDUCTION
SKIN
GRAFTS
GRAFT-HOST REACTION
IMMUNOSUPPRESSION
LYMPHOCYTES
MICE
MONOCLONAL ANTIBODIES
RADIATION CHIMERAS
THYMUS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
HEMATOPOIETIC SYSTEM
LEUKOCYTES
LYMPHATIC SYSTEM
MAMMALS
MATERIALS
MOSAICISM
ORGANS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals