Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes

Abstract

The ability of herpes simplex virus (HSV)-specific, cytotoxic T lymphocytes to mediate recovery of mice lethally infected with HSV was examined. Adoptive transfer of splenocytes from mice that had been primed in vivo with HSV and restimulated with HSV in vitro protected lethally infected normal and cyclophosphamide-immunosuppressed mice from death. In contrast, equal numbers of normal splenocytes or immune splenocytes cultured without antigen failed to mediate recovery. Recovery was also transferred by noncultured, primary immune splenocytes, although the protective efficacy of these cells was 10-fold less than when immune splenocytes restimulated in vitro were used. Treatment of the cells with anti-Thy 1 or anti-Lyt 2.1 plus complement before adoptive transfer abrogated recovery. No decrease in protection was seen when in vitro-restimulated splenocytes were treated with anti-Lyt 1.1 plus complement. Splenocytes expression natural killer activity also failed to effect recovery. The administration of hyperimmune anti-HSV antibody to normal, immunocompetent mice resulted in recovery, whereas no significant protection of immunosuppressed mice by anti-HSV was observed. When antibody was given concurrently with cultured immune splenocytes, the percentage of mice that recovered from infection was greater than that seen with either antibody or cultured immune splenocytes alone. These experiments demonstrate that Lyt 2-positive cells with cytotoxic activity generated by in vitro immunization can mediate recovery from lethal HSV infection, whereas, under the conditions chosen, Lyt 1-positive cells were unable to mediate recovery.