Immune responses to herpes simplex virus in patients with recurrent herpes labialis: I. Development of cell-mediated cytotoxic responses.

Groups of subjects during acute (0-3 days) and convalescent (2-3 weeks) phase of recurrent herpes labialis (RHL), and other subjects seropositive or seronegative for herpes simplex virus type 1 (HSV-1) antibody without any history of RHL, were tested for the appearance of cell-mediated cytotoxic responses by stimulating peripheral blood leukocytes (PBL) in vitro with ultraviolet-inactivated HSV-1 antigen, using the release of radiolabelled chromium (51Cr) from HSV-1-infected autologous, or allogeneic lymphocytes and K562 erythroleukemia cell line as nonspecific targets. Development of HSV specific cytotoxic response using autologous targets was essentially limited to subjects with RHL and in HSV antibody seropositive control subjects. Peak activity was observed during the acute phase of the disease, compared to the activity in the convalescent phase in seropositive subjects with RHL, and was preceded by high lymphoproliferative response to HSV. Higher cytotoxic responses against K562 cells were also observed in RHL subjects compared to the controls. Depletion of Leu-2+, Leu-3+ or Leu-11 effector lymphocytes from HSV-1-stimulated PBL cultures by treatment with complement and appropriate monoclonal antibodies resulted in significant reduction of cytotoxicity to HSV-1-infected autologous cells. However, cytotoxicity to K562 cells was reduced only after depletion of Leu-11+ cells. Low levels of allogeneic restriction were observed for cytotoxicity to HSV-1-infected targets. These observations suggest selective activation of virus specific Leu-2+ and Leu-3+ T cell subsets as well as natural killer cell mediated cytotoxic mechanisms during the active phase of recurrences of herpes simplex virus infection.