Immunotherapy for Virus Infection

Abstract

Understanding of virus-induced immune response disease and the related immunopathology has its roots in the studies reported by Rowe (1954). He showed that suppression of immune responses changed the ordinarily lethal, acute infection with lymphocytic choriomeningitis virus (LCMV) to a persistent infection in susceptible mice. The subsequent work of many investigators who used neonatal thymectomy, genetically athymic mice, irradiation, antilymphoid drugs, or antithymocyte sera, etc. (reviewed in Buchmeeer et al. 1980) extended the concept of immune response-mediated injury during viral infection. Thereafter, the role of lymphocytes in mediating virus-induced immunologic injury was delineated. First, experiments performed independently by Lundstedt (1969) and Oldstone et al. (1969) showed that lymphocytes obtained 6–9 days after an acute LCMV infection or primary inoculation killed LCMV-infected targets in vitro. Next, such lymphocytes were found to be of thymic origin and to bear Thy 1.2 markers of their surfaces (Cole et al. 1973; Marker and Volkert 1973). Gilden et al. (1972a, b) showed that mice which survived an ordinarily lethal dose of LCMV owing to immunosuppression developed acute lymphocytic choriomeningitis (LCM) disease and died when reconstituted with syngeneic, immune T-lymphocytes. Zinkernagel and Doherty (1974 a) defined the need for two signals between the cytolytic T-lymphocyte and its infected target, namely, virus specificity and H-2 restriction, so that killing of LCMV-infected cells could proceed.