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Transplantation. 2007 Sep 15;84(5):619-28.

Liver allografts are toleragenic in rats conditioned with posttransplant total lymphoid irradiation.

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1
Department of Surgery, Division of Transplantation, Stanford University School of Medicine, Stanford, CA, USA.

Abstract

BACKGROUND:

Posttransplant total lymphoid irradiation (TLI) treatment has been applied to tolerance induction protocols in heart and kidney transplantation models.

METHODS:

We examined the efficacy and mechanism of posttransplant TLI treatment in the induction and maintenance of tolerance in a rat orthotopic liver transplantation model.

RESULTS:

Posttransplant TLI prolonged ACI (RT1(a)) liver allograft survival in Lewis (RT1(b)) hosts, with 50% long-term engraftment without immunosuppression and without evidence of chronic rejection. Injection of donor-type liver mononuclear cells (LMCs) facilitated the prolongation of graft survival, with more than 70% of grafts in LMC recipients surviving more than 100 days without chronic rejection. Recipients with long-term liver allograft survival accepted ACI but not PVG skin grafts. In TLI-conditioned recipients with accepted grafts, apoptosis occurred predominantly in graft-infiltrating leukocytes. In contrast, there were few apoptotic leukocytes in rejecting grafts. Recipients with long-term graft acceptance (>100 days of survival) demonstrated evidence of immune deviation; mixed lymphocyte reaction to ACI stimulator cells was vigorous, but secretion of interferon-gamma and interleukin-2 was reduced. In tolerant recipients, the number of Foxp3(+) CD25(+) CD4(+) regulatory T cells was increased in the liver allograft as well as in the peripheral blood.

CONCLUSION:

We conclude that posttransplant TLI induces tolerance to liver allografts via a mechanism involving apoptotic cell-deletion and immunoregulation.

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