Cytokine profile of liver- and blood-derived nonspecific T cells after liver transplantation: T helper cells type 1/0 lymphokines dominate in recurrent hepatitis C virus infection and rejection

Orthotopic liver transplantation (OLT) is a successful treatment in patient s with hepatitis C virus (HCV)associated end-stage liver disease worldwide. T lymphocytes and their cytokines are believed to have a pivotal role in t he defense against HCV and in allograft rejection. An immunosuppressive dru g regimen may cause a cytokine imbalance toward a T helper (TH) cell type 2 profile that is associated with the persistence of infection and acceptanc e of the graft. The aim of this study is to assess whether cytokine imbalan ces toward a TH1- or TH2-type response may have a role in recurrent HCV inf ection and rejection after OLT. Twenty-one intrahepatic T-cell lines of 15 patients with recurrent HCV infection after OLT (group A) and 15 lines of 1 1 patients with rejection (group B) were studied. Both patient groups had r eceived liver allografts because of HCV-associated end-stage liver disease. Patients with HCV-induced liver disease who did not undergo OLT served as controls: 17 patients with chronic hepatitis C (CH-C) and 8 patients with c irrhosis. At the time of liver biopsy, 14 blood-derived T-cell lines of 12 patients with recurrent HCV infection, 7 of 10 patients with rejection, and 18 of 18 control patients were also investigated. Regardless of the underl ying disease (recurrent HCV infection, rejection, HCV-induced hepatitis, an d cirrhosis), all fiver tissue-derived T-cell lines produced interferon-gam ma; some additionally produced interleukin-4 (IL-4), bur none produced IL-1 0, indicating that the TH0/1 cytokine profile dominates. T-cell lines showi ng a Till cytokine profile derived from intrahepatic T cells could be estab lished significantly more often in recurrent HCV infection and rejection th an in controls with CH-C (Fisher's exact test, P<.05). The cytokine profile of intrahepatic T cells did not differ from that obtained in peripheral bl ood. TH0/1 cytokine profile dominates the intrahepatic and blood-derived im mune response in recurrent HCV infection and rejection after OLT regardless of the mode of immunosuppression. The lymphokine profile of immunocompromi sed patients with recurrent HCV infection or rejection does not differ prin cipally from that of patients with HCV-induced hepatitis and cirrhosis, but seems to show a Till profile significantly more often. Copyright (C) 2000 by the American Association for the Stimy of Liver Diseases.