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J Immunol. 2006 Jul 15;177(2):863-8.

Targeted lymphoid homing of dendritic cells is required for prolongation of allograft survival.

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  • 1Transplantation Research Laboratory, Division of Transplantation, Department of Surgery, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143.

Abstract

Accumulating evidence that dendritic cells (DC) are important regulators of peripheral immune tolerance has led to the concept that donor-derived DC may be useful for inducing donor-specific transplantation tolerance. Although in vitro studies in this field have been encouraging, in vivo results have been inconsistent. Recent evidence has suggested a critical role of lymphoid organs in tolerance induction. In this study, we use a novel gene transduction technique to show that engineered expression of CCR7 on immature DC can markedly increase DC homing to lymphoid organs, leading to increased interaction with Ag-specific T cells. Moreover, we show that a single infusion of DC coexpressing CCR7 and the immunomodulatory molecule viral IL-10 (vIL-10) markedly prolongs cardiac allograft survival (mean survival time >100 days); importantly, DC expressing either vIL-10 alone or CCR7 alone was not effective. These results demonstrate an important paradigm for immune modulation using DC.

PMID:
16818740
[PubMed - indexed for MEDLINE]
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