Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen
Journal Article
·
· J. Exp. Med.; (United States)
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), Journal Name: J. Exp. Med.; (United States) Vol. 169:2; ISSN JEMEA
- Country of Publication:
- United States
- Language:
- English
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Journal Article
·
Sat Jun 01 00:00:00 EDT 1991
· Transplantation; (United States)
·
OSTI ID:5505809
Specific tolerance induction across a xenogeneic barrier: Production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen
Journal Article
·
Sun Jul 01 00:00:00 EDT 1990
· Journal of Experimental Medicine; (USA)
·
OSTI ID:6644391
Mixed chimerism to induce tolerance for solid organ transplantation
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Sun Mar 31 23:00:00 EST 1991
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·
OSTI ID:5315038
Related Subjects
560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CHIMERAS
CONNECTIVE TISSUE CELLS
GRAFT-HOST REACTION
GRAFTS
HEMATOPOIETIC SYSTEM
IMMUNITY
IMMUNOSUPPRESSION
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MONOCLONAL ANTIBODIES
MOSAICISM
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RODENTS
SKIN
SOMATIC CELLS
THYMUS
TISSUES
TRANSPLANTS
VERTEBRATES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CHIMERAS
CONNECTIVE TISSUE CELLS
GRAFT-HOST REACTION
GRAFTS
HEMATOPOIETIC SYSTEM
IMMUNITY
IMMUNOSUPPRESSION
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MONOCLONAL ANTIBODIES
MOSAICISM
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RODENTS
SKIN
SOMATIC CELLS
THYMUS
TISSUES
TRANSPLANTS
VERTEBRATES