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- W2021036686 abstract "A SELECTED population of patients with intestinal failure and unable to support the iatrogenic consequences of long-term parenteral nutrition would greatly benefit from intestinal transplantation. Despite preliminary trials to establish this technique, early graft loss and subsequent infections are very common, and the clinical result has been very deceptive.’ Better than aggressive, general immunosuppression therapies, the implementation of more selective, toleranceinducing, therapies also represents a current challenge in the field of clinical transplantation. Recently and in various models related to solid organ transplants and autoimmunity, the intrathymic (IT) injection of donor-derived cells/ Ags (or autologous targets in the case of autoimmunity) has been shown efficient in the induction of Ag-specific tolerance.2-4 The rational of this manipulation is based in the attempt to negatively select the newly emerging alloreactive T-cell specificities when confronted with their targets, as it happens normally inside the thymus.” We present some preliminary findings in a new experimental system of heterotopic intestinal grafts and IT injections of donor-derived cells (splenocytes + bone marrow cells) in inbred mouse strains. The experimental groups have been also submitted to several combinations of lethal X-radiation and syngenic bone marrow (BM) transplantation and to short courses of parenteral cyclosporine A (CyA). The evolution of grafted tissues, quantification of the degree of peripheral chimerism, and modification of allospecific T-cytotoxic lymphocytes have been evaluated during 3 to 4 month periods of follow-up. Very high percentages of donor MHC class I-positive cells are present in the periphery, but not inside the thymus, of the grafted mice for at least 2 to 3 months. Surprisingly, the presence of injected cells inside the thymus is undetectable after 1 week of the IT manipulation. Also, clonal deletion of recipient thymocytes reacting against donor-derived superantigens (Mls-la) is not observed. The vast majority of chimeric cells represent (Ag-presenting) dendritic cells, likely coming from both the grafted intestine and the IT inoculum. Allospecific T-cell cytotoxic reactivities are significantly reduced in the mice receiving IT injections. This suggests" @default.
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- W2021036686 date "1997-02-01" @default.
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- W2021036686 title "Induction of peripheral chimerism in an allogenic model of small bowel transplantation with intrathymic inoculation of donor-derived cells" @default.
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- W2021036686 doi "https://doi.org/10.1016/s0041-1345(96)00403-4" @default.
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