Allopeptide-pulsed dendritic cells and composite tissue allograft survival.
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.
Nguyen
Vu T
VT
Department of Surgery, University of Pittsburgh, PA, USA.
Taieb
Aurele
A
Sacks
Justin M
JM
Unadkat
Jignesh V
JV
Clavijo
Julio A
JA
Kim
Haena
H
Feili-Hariri
Maryam
M
Lee
W P Andrew
WP
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
D010455:Peptides