DEPLETION OF CD8(-LYMPHOCYTES BY MURINE MONOCLONAL CD8 ANTIBODIES ANDRESTORED SPECIFIC T-CELL PROLIFERATION IN-VIVO IN A PATIENT WITH CHRONIC HEPATITIS-C() T)

Cellular immune mechanisms, especially those mediated by CD8(+) T cell s, are important in the pathogenesis and control of viral infections. On the other hand, as shown for chronic lymphocytic choriomeningitis v irus infection in the mouse, CD8(+) T cells may not only hinder the el imination of a virus, but make the host unresponsive to a second viral infection, In hepatitis C virus (HCV) infections, at least 50% of the patients become chronically infected, despite the detection of HCV-sp ecific CTL and a specific proliferative response to HCV Ags in PBL and in lymphocytes isolated from the liver, To better understand the immu nopathologic mechanisms of CD8(+) cells in vivo and to search for a po tential treatment, we applied murine CD8 mAbs to a patient with therap y-resistant chronic HCV. A drastic reduction of CD8(+) circulating lym phocytes, a reduction of CD8 molecule density, and complement fixation on CD8(+) cells were observed, The reduction of CD8(+) cells was comp ensated partially by an elevation of CD4(+) cells. High concentrations of neutralizing human anti-mouse Abs were induced, After the Ab infus ions, the CD4/CD8 ratio In peripheral blood increased from 1.6 to valu es of about 3 during therapy, and gradually decreased to 2.3 1 yr afte r the last mAb infusion. A continuing decrease of serum aminotransfera ses and clinical improvement was observed, Interestingly, after initia tion of treatment, a significant proliferative response to HCV-specifi c Ags became measurable.