Specific tolerance induction across a xenogeneic barrier: Production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

Journal Article · Sun Jul 01 04:00:00 EDT 1990 · Journal of Experimental Medicine; (USA)

DOI:https://doi.org/10.1084/jem.172.1.195· OSTI ID:6644391

Sharabi, Y; Aksentijevich, I; Sundt, T.M. 3d.; Sachs, D H; Sykes, M ^[1]

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1. National Cancer Institute, Bethesda, MD (USA)

The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipients with monoclonal antibodies (mAbs) against NK1.1, Thy-1.2, CD4 and CD8, followed by administration of 3 Gy whole body radiation (WBI), 7 Gy thymic irradiation, and infusion of T cell-depleted rat bone marrow cells (BMC). Rat cells appeared among peripheral blood lymphocytes (PBL) of such recipients by 2-3 wk, and rat T cells by 2-5 wk following bone marrow transplantation (BMT). Donor-type rat skin grafts placed 4 mo after BMT were accepted, while simultaneously placed non-donor-type rat skin grafts were promptly rejected. In addition to its clinical potential, the ability to induce donor-specific tolerance across xenogeneic barriers using such a nonlethal preparative regimen provides a valuable model for the study of mechanisms of xenogeneic transplantation tolerance.

• OSTI ID: 6644391
• Journal Information: Journal of Experimental Medicine; (USA), Journal Name: Journal of Experimental Medicine; (USA) Vol. 172:1; ISSN JEMEA; ISSN 0022-1007
• Country of Publication: United States
• Language: English

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560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIBODIES
ANTIGENS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW CELLS
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LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MONOCLONAL ANTIBODIES
MOSAICISM
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RATS
RODENTS
SKIN
SOMATIC CELLS
STEM CELLS
SURVIVAL TIME
THYMUS
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WHOLE-BODY IRRADIATION