GENERATION OF CYTOTOXIC T LYMPHOCYTES DURING COXSACKIE-VIRUS B-3 INFECTION .2. CHARACTERIZATION OF EFFECTOR CELLS AND DEMONSTRATION OF CYTOTOXICITY AGAINST VIRAL-INFECTED MYOFIBERS

Abstract

The virus-specific cytotoxic effector cells which are present in the spleens of mice 7 days after infection with Coxsackievirus B-3 were characterized. An in vitro 51Cr assay employing syngeneic virus-infected neonatal fibroblasts was used to measure cytotoxic activity. Treatment of immune cells with (anti-thy-1.2) and complement abolished their cytotoxic activity, but no reduction occurred when B [bone marrow-derived] cells were removed by incubation with anti-Ig [immunoglobulin] and complement or macrophages eliminated by adherence depletion. The cytotoxic reaction was probably mediated by sensitized T [thymus-derived] cells; B cells and macrophages probably did not play an important role. Reciprocal assays performed with BALB/c and CBA/J cells showed that Coxsackievirus-immune spleen cells lysed infected syngeneic targets but not allogeneic targets, showing that cytotoxicity was mediated by effector T cells. An in vitro assay system employing neonatal myocardial cells was developed and used to show that Coxsackievirus-infected myofibers were susceptible to destruction by immune spleen cells. Mice infected with Coxsackie B viruses are apparently able to mount a cell-mediated immune response with production of cytotoxic T cells which have the capacity to damage tissues infected with these agents.