title: Donor-specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft.
abstract: This study examined whether a heart or kidney graft could provide protection for the more resistant skin graft. Buffalo rat recipients were given a single dose of RIB 5/2 (non-depleting anti-CD4 mAb) plus i.v. Lewis splenocytes 21 days before being given Lewis heart or kidney grafts. Lewis skin was grafted either simultaneously with, or after, long-term (>50 days) Lewis heart or kidney allograft acceptance. Immune responsiveness was analyzed by in vitro mixed lymphocyte culture (MLC), cytotoxic T lymphocytes (CTLs), and limiting dilution analysis (LDA). While i.v. alloantigen plus RIB 5/2 resulted in long-term acceptance of heart and kidney, survival of skin grafts alone was not prolonged. However, simultaneous transplantation with kidney, but not heart, resulted in long-term skin graft acceptance, while skin grafts subsequently grafted to recipients tolerant to kidney or heart were not accepted. In vitro analysis revealed a down-regulation of proliferation, cytotoxicity, and precursor T-helper cells (pThs)/precursor cytotoxic T lymphocytes (pCTLs) in Buffalo recipients accepting Lewis kidney and skin allografts. While RIB 5/2 plus Lewis splenocytes do not prolong the survival of skin grafts, Lewis skin grafted simultaneously with a kidney, but not heart, is accepted indefinitely and provides donor-specific protection for a subsequent skin graft.
authors.affiliation: Department of Surgery, Washington University School of Medicine, Suite 5103, One Barnes-Jewish Hospital Plaza, St. Louis, MO 63110, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Margenthaler
authors.forename: Samuel
authors.initials: S
authors.lastname: Yu
authors.forename: Naoki
authors.initials: N
authors.lastname: Otomo
authors.forename: Manfred
authors.initials: M
authors.lastname: Lehmann
authors.forename: M Wayne
authors.initials: MW
authors.lastname: Flye
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000502:physiology*; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous