MECHANISM OF TOLERANCE FOLLOWING CLASS-I DISPARATE RENAL-ALLOGRAFTS IN MINIATURE SWINE - CELLULAR-RESPONSES OF TOLERANT ANIMALS

Previous studies utilizing a recombinant MHC haplo- type in our partially inbred miniature swine herd have demonstrated that some recipients matched only for SLA class II show long-term acceptance of renal allografts without exogenous immunosuppression. Such animals have been shown to develop systemic tolerance as evidenced by prolonged rejection times of subsequent donor-specific, but not third-party, skin grafts. In the present studies in vitro cellular responses of long-term tolerant animals and of 7 animals studied sequentially are presented. Long-term tolerant animals demonstrated responses consistent with the absence of the class reactive helper populations normally present in naive controls. Animals studied sequentially segregated into two groups based on cellular reactivity and survival. All animals showed complete loss of antidonor class I cell- mediated lymphocytolytic (CML) reactivity by postoperative day 10. However, animals surviving <20 days maintained CML reactivity to donor class I plus third- party class II in the posttransplant period, while animals surviving >40 days lost such reactivity. Addition of exogenous interleukin 2 could not reverse this loss. These studies suggest that tolerance induction to a renal allograft across a class I only difference involves effects on both helper and killer class I reactive cell populations. © 1990 by Williams & Wilkins.