| Cardiac allograft survival across major histocompatibility complex barriers in the rhesus monkey following T lymphocyte-depleted autologous marrow transplantation. II. Prolonged allograft survival with extensive marrow T cell depletion. | |
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MedLine Citation:
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PMID: 2646775 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present study, we tested the possibility that a vascularized allograft might induce immunological tolerance in a myeloablated host, similar to the tolerance induced by allogeneic bone marrow grafts. To this end, we developed a rhesus monkey model consisting of myeloablative total-body irradiation and T cell-depleted autologous marrow transplantation followed by MHC-mismatched heterotopic cardiac allograft implantation. Limiting dilution analysis was used to quantify residual marrow T cells following depletion. We found that (1) allograft survival was substantially prolonged in the absence of immunosuppressive drugs (median survival = 160 days) over that seen in controls treated identically but receiving non-T cell-depleted marrow (median survival = 14 days); (2) there was a correlation between allograft survival prolongation and the extent of marrow T cell depletion, with a maximum survival of 329 days associated with a residual marrow T cell content of 0.00014%; (3) nonspecific immune deficiency--and, possibly, specific unresponsiveness of limited duration (determined by cryopreserved donor and third-party skin grafting)--contributed to the rejection-free period seen in recipients of extensively depleted marrow; (4) late allograft rejection occurred in 3 of 3 long-term survivors, thereby demonstrating that permanent tolerance was not induced by the allograft across MHC barriers; and (5) as few as 1.4 x 10(4) infused marrow T cells/kg were sufficient to mediate acute allograft rejection, a threshold approximately 10-fold lower than that reported for the induction of acute graft-versus-host disease following allogeneic bone marrow transplantation. |
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Authors:
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R D Moses; K S Orr; J D Bacher; D H Sachs; R E Clark; R E Gress |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Transplantation Volume: 47 ISSN: 0041-1337 ISO Abbreviation: Transplantation Publication Date: 1989 Mar |
Date Detail:
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Created Date: 1989-04-14 Completed Date: 1989-04-14 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0132144 Medline TA: Transplantation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 435-44 Citation Subset: IM |
Affiliation:
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Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Marrow Transplantation* Female Graft Survival Heart Transplantation* Lymphocyte Depletion Macaca mulatta Major Histocompatibility Complex Male Skin Transplantation T-Lymphocytes Transplantation, Homologous Whole-Body Irradiation |
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