DONOR-SPECIFIC HYPOREACTIVITY AFTER LIVER-TRANSPLANTATION - PROMINENTDECREASES IN DONOR-SPECIFIC CYTOTOXIC T-LYMPHOCYTE PRECURSOR FREQUENCIES INDEPENDENT OF CHANGES IN HELPER T-LYMPHOCYTE PRECURSOR FREQUENCIES OR SUPPRESSOR-CELL ACTIVITY

Background. The development of immunological donor-specific hyporeacti vity may account for the low incidence of chronic rejection after clin ical liver transplantation. We investigated whether hyporeactivity com monly develops after liver transplantation by analyzing precursor freq uencies of donor-reactive cytotoxic (CTLp) and helper (HTLp) T lymphoc ytes and mixed lymphocyte culture (MLC) reactivity in liver allograft recipients. We further studied whether CTLp hyporeactivity correlated with changes in donor-specific HTLp frequencies or suppressor cell act ivity. Methods. CTLp and HTLp frequencies and MLC reactivity against d onor and third-party spleen cells were determined in pre- and posttran splantation peripheral blood samples from 18 recipients with good graf t function 2 years after transplantation. By mixing posttransplantatio n samples (with ''putative'' suppressor cell activity) with pretranspl antation samples tin which normal CTL activity with no suppressor cell activity is expected), the presence of suppressor cell activity in pe ripheral blood was analyzed. Results. Two years after transplantation, all but one (94%) of the recipients had developed CTLp hyporeactivity as evidenced by reduced donor-specific CTLp frequencies. The developm ent of hyporeactivity was not specific for any particular underlying d isease. The occurrence of HTL hyporeactivity, however, was less freque nt: 38% and 20% of recipients were HTLp and MLC hyporeactive, respecti vely. Decreases in CTLp frequencies did not correlate with decreased d onor-specific HTL function or suppressor cell activity in peripheral b lood samples. Conclusions. Donor-specific CTLp hyporeactivity can deve lop in the majority of liver allograft recipients, irrespective of und erlying disease. Donor-specific HTL hyporeactivity, however, occurs in frequently. A reduction in donor-specific CTLp frequencies was found t o be independent of changes in donor-specific HTLp or suppressor cell activity, suggesting that other mechanisms (e.g., clonal deletion) are operative in the reduction of donor-specific CTLp after liver transpl antation.