Induction of Cellular Immunity to Herpes Simplex Virus: Relationship to the Humoral Immune Response

Abstract

Abstract In vitro lymphocyte stimulation and virus-neutralization techniques were employed to study the relationship between the cellular and humoral immune responses to herpes simplex virus (HSV) in rabbits. Lymphocytes specifically sensitized to HSV were detected as early as 3 days after infection, generally before the appearance of neutralizing antibody. Neutralizing antibody levels continued to rise over the next several weeks, whereas the ability of sensitized lymphocytes to respond to viral antigens markedly decreased. Reinfection 60 days after the primary infection resulted in a sharp increase in the responsiveness of the lymphocytes to viral antigens. The induction of cell-mediated immunity and the responsiveness of sensitized lymphocytes to viral antigens appears to be intimately related to the physical state of the virus. Animals inoculated with infectious HSV developed both cellular and humoral immunity; animals inoculated with UV-inactivated HSV developed a cellular immune response, but little if any neutralizing antibody; animals inoculated with HSV complexed with anti-HSV antibody developed neither a cellular nor a humoral immune response. In vitro, specifically sensitized lymphocytes could be stimulated by virus and by virus bound to cells, but not by cell-bound virus that had been incubated with antiviral antibody. These observations suggest that antiviral antibody can affect both the induction of cell-mediated immunity and the responsiveness of specifically sensitized lymphocytes to viral antigens bound to cells.