Donor-specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft

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.