DONOR-SPECIFIC STIMULATION OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROMRECIPIENTS OF ORTHOTOPIC LIVER-TRANSPLANTS IS ASSOCIATED, IN THE ABSENCE OF REJECTION, WITH TYPE-2 CYTOKINE PRODUCTION

In this study, we examined the cytokine production by human peripheral blood mononuclear cells (PBM) from recipients of orthotopic liver tra nsplants which had been stimulated by donor-specific alloantigen. Leve ls of interleukin (IL)-2, IL-4, interferon (IFN)-gamma, IL-IO and tran sforming growth factor (TGF)-beta produced in vitro from PBM of 15 tra nsplant recipients at 5-7 months post transplantation were analysed af ter donor-specific, third-party, or non-specific stimulation. Mononucl ear cell proliferation in response to stimulation and cytokine mRNA fr om the cell cultures were assayed. Donor-specific antigen was obtained from donor spleen cells which had been obtained and frozen in liquid nitrogen at the time of organ retrieval. Third-party restimulation use d equivalent numbers of spleen cells pooled from the other 14 organ do nors. Cytokine production was correlated with the clinical condition o f the patient, including biopsy results when available, and biochemica l data. The data show a highly significant correlation between the don or-specific- and third-party- stimulated IL-4 and IL-10 production fro m recipient PBM with stable liver graft function as assessed by histop athology and/or biochemistry. This correlation was independent of leve l of immunosuppression. These data strongly support a role for IL-4 an d/or IL-IO in the induction and/or maintenance of tolerance to human l iver allografts. Measurement of the levels of these cytokines from rec ipient PBM after donor-specific antigen stimulation in vitro may be a useful test for monitoring for acute allograft rejection. (C) 1998 Els evier Science B.V. All rights reserved.