Critical issues emerging from current attempts at inducing transplantation tolerance in the clinic include the need for biomarkers that predict and diagnose tolerance as well as for the identification of barriers to tolerance induction and maintenance. Our preliminary observations have led us to the realization that the durability of the tolerant state is variable and can be unpredictably breached by Listeria infections. The overall goal of the proposed studies Is to determine a mechanistic basis for how Infections can either erode or transiently abrogate robust tolerance after It has been stably established.
(Relevance) Successful induction of transplantation tolerance for achieving long-term allograft survival has been reported in a number of preclinical models and in limited clinical scenarios. 777e overall goal of the proposed studies Is to determine a mechanistic basis for how infections with Listeria and other Infections erode or abrogate tolerance after It has been well and stably established through co-stimulation blockade. Insights gained from these studies may lead to new approaches for establishing, maintaining and restoring the state of tolerance in transplantation.
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