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Critical Reviews™ in Immunology

Impact factor: 3.889

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v28.i5.30
pages 403-439

Role of Innate Immunity in Transplantation Tolerance

David M. Miller
Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655
Aldo A. Rossini
Division of Diabetes, Department of Medicine and the Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655
Dale L. Greiner
Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655

ABSTRACT

Allogeneic organ transplantation has proven to be an effective therapeutic strategy for patients with end-stage organ disease. However, the chronic immunosuppression that is required for the survival of the allograft increases the risk for infection and malignancy. The establishment of transplantation tolerance, defined functionally as the survival of a donor allograft in the absence of immunosuppression, is the ultimate goal in the field of transplantation. Transplantation tolerance can be achieved using approaches that induce peripheral and/or central tolerance to the allograft. Protocols based on costimulation blockade (CB) have emerged as some of the most promising protocols for inducing long-term allograft survival in the absence of chronic immunosuppression. Despite its potential, recent evidence suggests that the efficacy of costimulation blockade can be reduced by environmental perturbations such as infection or inflammation, which activate Toll-like receptors (TLR). In this review, we discuss how the activation of TLRs can affect the induction and maintenance of transplantation tolerance.