Assessment of peripheral tolerance in anti-CD4 treated C57BL/6 mouse hearttransplants recipients

The study was designed to compare second heart and skin grafts and in vitro assays as a means of assessing peripheral tolerance in C57BL/6 mice. Vascu larized heterotopic BALB/c hearts were placed in C57BL/6 recipients treated with anti-CD4, GK1.5 (1 mg total per 20 g mouse i.p. on days 0, 1, 2, 3). Those mice in which hearts survived for >60 days were challenged with donor and third-party (CBA) skin grafts or with second heart grafts, of donor or third-party origin, attached to the carotid artery and jugular vein. In vi tro alloreactivity was assessed by mixed lymphocyte reactions (MLR) and cel l mediated lympholysis (CML) using recipient spleen cells. Parenchymal dama ge, cellular infiltration and vascular disease were assessed from the histo logy of long-term allografts and isografts. Allografts in untreated recipients were rapidly rejected while isografts su rvived > 100 days. Primary allografts in anti-CD4 treated recipients also s urvived > 100 days, as did donor strain secondary heart transplants given a t >60 days after the first graft. Third-party hearts were rapidly rejected, as were donor and third-party skin grafts placed on recipients with long-t erm allografts. These recipients showed low MLR response to both donor and third-party stimulators and donor-specific suppression of CML at 60 days po st graft. Long-surviving heart allografts all showed evidence of parenchyma l damage and vascular intimal thickening. Thus in the BALB/c to C57BL/6 don or-recipient strain combination, hearts, but not skin grafts, could be used to demonstrate peripheral tolerance, which seemed to be both organ and maj or histocompatibility complex (MHC) specific. Despite long survival, BALB/c hearts all showed evidence of parenchymal damage and vascular intimal thic kening, a sign of chronic rejection.