Open AccessDonor‐specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft
Author(s) -
Margenthaler Julie A.,
Yu Samuel,
Otomo Naoki,
Lehmann Manfred,
Flye M. Wayne
Publication year - 2003
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2003.tb00229.x
Subject(s) - medicine , kidney , splenocyte , mixed lymphocyte reaction , cytotoxic t cell , heart transplantation , transplantation , immunology , immune system , in vitro , surgery , t cell , biology , biochemistry
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.