Immune Response to Herpes Simplex Virus in Patients with Recurrent Herpes Labialis. II. Relationship between Interferon Production and Cytotoxic Responses

ABSTRACT. The relationship between the development of cytotoxic cellular immune response to herpes simplex virus type I (HSV-1)-infected autologous cells and the production of interferon (IFN) was studied using in vitro secondary sensitization of peripheral blood leukocytes in subjects with recurrent herpes labialis (RHL) and in normal controls without any history of recurrent herpes labialis. There was a significant discordance between optimal HSV-1 antigen dose required for induction of peak cytotoxic responses and for maximal activity of IFN. Moderate IFN activity (6–100 U/ml) was demonstrated in all HSV-1 antigen-stimulated peripheral blood leukocytes collected from subjects during both acute and convalescent phase of RHL. However, only 50% of seropositive controls and no seronegative controls exhibited detectable IFN activity, when stimulated with HSV-1 antigen, although such in vitro stimulation resulted in maximal virus-specific cell-mediated cytotoxicity. A correlation of virus specific cytotoxic activity to HSV-1 and IFN production (r = 0.38, p < 0.05) was less marked than that of cytotoxic activity to K562 (natural killer-sensitive target cells) and IFN titer (r = 0.48, p < 0.01). Furthermore significant reverse correlations between cytotoxicity against HSV-1-infected autologous cells and a titer of ?-IFN was observed in samples with high cytotoxic activity. These observations suggest that ?-IFN produced by HSV immune T cell may also act as an autoregulatory factor against the production of cytotoxic cellular activity against HSV-1-infected autologous cells.