Human allograft acceptance is associated with immune regulation

The ultimate goal of transplantation is drug-free allograft acceptance, whi ch is rarely encountered in transplant recipients. Using a novel human-to-m ouse "trans vivo" delayed-type hypersensitivity assay, we assessed donor-re active cell-mediated immune responses in kidney and liver transplant patien ts, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the other s (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patie nts D.S., R.D., and M.L. responded strongly to recall, but not donor, antig ens. Furthermore, when donor and recall antigens were colocalized, the reca ll response in these three patients was inhibited. This donor antigen-linke d nonresponsiveness was observed in four other patients who are still maint ained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relie s on either TGF-beta or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immu ne regulation pattern, which may be useful in the diagnosis and/or monitori ng of transplant patients for allograft acceptance.