title: Targeted lymphoid homing of dendritic cells is required for prolongation of allograft survival.
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.
authors.affiliation: Transplantation Research Laboratory, Division of Transplantation, Department of Surgery, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143.
authors.forename: Kym R
authors.initials: KR
authors.lastname: Garrod
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Chang
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Liu
authors.forename: Todd V
authors.initials: TV
authors.lastname: Brennan
authors.forename: Robert D
authors.initials: RD
authors.lastname: Foster
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic; D023001:Transplantation Tolerance / Q000235:genetics
chemical_list: C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016753:Interleukin-10