Targeted lymphoid homing of dendritic cells is required for prolongation of allograft survival.
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.
Garrod
Kym R
KR
Transplantation Research Laboratory, Division of Transplantation, Department of Surgery, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143.
Chang
Catherine K
CK
Liu
Feng-Chun
FC
Brennan
Todd V
TV
Foster
Robert D
RD
Kang
Sang-Mo
SM
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
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016753:Interleukin-10