Liver Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Induction of long-term graft acceptance by a combination treatment of donor splenocytes and CTLA4Ig in a high responder rat liver transplantation model.

Schmitz V, Neumann UP, Fischer U, Langrehr J, Neuhaus P

Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow, Augustenburger Platz, Berlin, Germany. volker.schmitz@uchsc.edu

The CTLA4Ig has led to an improved survival rate in various allograft transplantation models. We investigated in a high responder rat model (Dark Agouti to Lewis) of orthotopic liver transplantation (ORLT), whether an additional adoptive cell transfer can enhance the effect of CTLA4Ig. After transplantation, recipients (n = 13/group) were treated with donor or third-party splenocytes alone or in combination with CTLA4Ig. Administration of splenocytes alone had no significant effect on survival (median 13 days, range 9-14) compared with untreated controls (median 10 days, range 8-12). CTLA4Ig monotherapy prolonged survival to a median of 30 days (range 11-150) but resulted in long-term graft rejection. The additional administration of third-party splenocytes showed no significant improvement over CTLA4Ig monotherapy. Only the combination of donor splenocytes with CTLA4Ig led to long-term graft acceptance (>150 days) without clinical and/or histological signs of rejection. A higher rate of apoptosis could be detected in livers at early time-points in long-term survivors receiving CTLA4Ig and donor splenocytes. Analysis of cytokine mRNA expression revealed a decrease of interleukin-2 at early time-points in all groups receiving CTLA4Ig; whereas, interferon-gamma was increased in long-term survivors receiving CTLA4Ig and donor cells or donor cells alone. The combination of CTLA4Ig and donor derived splenocytes is potent to induce long-term survival and graft acceptance. The mechanisms appear to involve the induction of an early inflammatory impulse and apoptosis.

Published 15 September 2005 in Transpl Int, 18(10): 1187-96.
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