title: Allopeptide-pulsed dendritic cells and composite tissue allograft survival.
abstract: Composite tissue allografts (CTAs) contain their own reservoir of vascularized bone marrow, offering novel aspects for the induction of donor-specific tolerance. Additionally, the manipulation of recipient dendritic cells, pulsed with donor allopeptide, has been shown to engender solid organ allograft survival. To exploit these modalities, we have developed a protocol utilizing injection of recipient bone marrow-derived dendritic cells (BMDCs) pulsed with a donor-derived peptide for use in CTA transplantation. Six days prior to orthotopic hind-limb transplantation, Lewis rats received IV injection of donor allopeptide-pulsed, recipient BMDCs, in conjunction with a single dose of anti-lymphocyte serum. Control groups displayed signs of allograft rejection within 5 days postoperatively. Animals within the primary experimental cohort demonstrated prolongation of graft survival to an average of 8 days, and exhibited low numbers of donor T cells. The use of BMDCs in conjunction with transient immunosuppression has potential therapeutic application for induction of donor-antigen-specific tolerance to hind limb allografts.
authors.affiliation: Department of Surgery, University of Pittsburgh, PA, USA.
authors.forename: Vu T
authors.initials: VT
authors.lastname: Nguyen
authors.forename: Aurele
authors.initials: A
authors.lastname: Taieb
authors.forename: Justin M
authors.initials: JM
authors.lastname: Sacks
authors.forename: Jignesh V
authors.initials: JV
authors.lastname: Unadkat
authors.forename: Julio A
authors.initials: JA
authors.lastname: Clavijo
authors.forename: Haena
authors.initials: H
authors.lastname: Kim
authors.forename: Maryam
authors.initials: M
authors.lastname: Feili-Hariri
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005269:Femur / Q000637:transplantation*; D006084:Graft Rejection / Q000503:physiopathology; D006085:Graft Survival; D008297:Male; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D019172:Transplantation Conditioning / Q000379:methods*; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D010455:Peptides