Tolerance, mixed chimerism, and chronic transplant arteriopathy.
نویسندگان
چکیده
Much evidence supports the conclusion that immunological responses to donor-specific incompatibilities are a major factor in producing "chronic" transplant rejection, including the arteriopathy (atherosclerosis) commonly present. Our experiments explored the effects of altered immunological responsiveness to these Ags on the formation of arteriopathy in transplanted mouse hearts. Specific immunological nonreactivity, or tolerance, was induced either by neonatal administration of allogeneic spleen cells (from F(1) donors between class I-mismatched donor and recipient strains), resulting in "classical" immunological tolerance, or by bone marrow infusion to suitably prepared adult recipients, either fully MHC mismatched or class I mismatched, yielding "mixed chimerism." Both approaches obviated systemic graft-versus-host effects. In both groups, donor-specific skin grafts survived perfectly and donor cell chimerism persisted. Specific Abs were undetectable in all recipients. Most transplants to either group of tolerant recipients developed striking vasculopathy in their coronary arteries (12 of 15 in neonatal tolerance and 15 of 23 in mixed chimeras). Neointimal infiltrates included CD4 and CD8 T cells and macrophages. Only 2 of 29 contemporary isotransplants showed any evidence of vasculopathy. Recipients essentially incapable of T and B cell responses (C.B-17/SCID and RAG1(-/-)) were also used. Transplants into these animals developed vasculopathy in 16 of 31 instances. Accordingly, in this setting, vasculopathy develops in the presence of H-2 gene-determined incompatibility even with minimal conventional immune reactivity. Perhaps innate responsiveness, that could include NK cell activity, can create such arteriopathic lesions. More evidence is being sought regarding this process.
منابع مشابه
Immuno-intervention for the induction of transplantation tolerance through mixed chimerism.
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The only way to overcome the need for life-long immunosuppression in a transplant recipient is to induce tolerance. Deletional tolerance can be reliably achieved with the induction of mixed chimerism through transplantation of donor bone marrow (BM). Despite the development of increasingly milder BM transplantation (BMT) animal models, BM engraftment in humans still requires considerably toxic ...
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عنوان ژورنال:
- Journal of immunology
دوره 167 10 شماره
صفحات -
تاریخ انتشار 2001