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 I 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 less than 20 days maintained CML reactivity to donor class I plus third-party class II in the posttransplant period, while animals surviving greater than 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.
Kortz
E O
EO
Immunology Branch, National Cancer Institute of Health, Bethesda, Maryland 20892.
Sakamoto
K
K
Suzuki
T
T
Guzzetta
P C
PC
Chester
C H
CH
Lunney
J K
JK
Sachs
D H
DH
D000818:Animals; D006085:Graft Survival / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D013552:Swine; D013556:Swine, Miniature / Q000276:immunology*; D013997:Time Factors
D015395:Histocompatibility Antigens Class I