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The Innate Immune System in Allograft Rejection and Tolerance¹

Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

As T cells alone are both necessary and sufficient for the rejection of virtually all allogeneic tissues, much of transplantation immunology has focused on cells of the adaptive immune system. During the past decade, advances in our understanding of innate responses to pathogen-associated molecules have spurred a "rediscovery" of innate immunity. Fueled by this, an increasing body of literature has emerged in which the role of the innate immune system in allograft rejection and tolerance has been examined more closely. This review will give an overview of recent studies and emerging concepts of how the cellular components of the innate immune system participate in the immune response to solid organ transplantation. These important studies highlight the complex interplay between diverse cells of the immune response and provide the basis for optimal strategies of tolerance induction.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Institutes of Health Grant R01-AI-062789 (to L.A.T.). D.F.L. is supported by National Institutes of Health Grant T32-HL-007586.

² Address correspondence and reprint requests to Dr. David F. LaRosa, University of Pennsylvania, 115 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104-6144. E-mail address: david.larosa{at}uphs.upenn.edu

³ Abbreviations used in this paper: PRR, pattern recognition receptor; DC, dendritic cell; HMGB1, high-mobility group box 1; NLR, NOD-like receptor; PMN, polymorphonuclear neutrophil; RAGE, receptor of advanced glycation end product; RLH, RIG-like helicase; Treg, regulatory T cell; TRIF, Toll/IL-1R domain-containing adaptor-inducing IFN-.