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

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

J Immunol

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

Published: July 2006

AI Article Synopsis

  • Dendritic cells (DC) are key players in regulating immune tolerance and could help achieve tolerance in organ transplants.
  • While lab studies have shown promise, real-life results vary, highlighting the role of lymphoid organs in this process.
  • The research demonstrates that modifying DC to express CCR7 and viral IL-10 significantly enhances organ transplant survival, suggesting a new approach for immune modulation.

Article 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.

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.177.2.863DOI Listing

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