Cell-mediated immunity in human herpesvirus infection: analysis by monoclonal antibodies

Peripheral blood lymphocytes (PBL) were obtained from heterosexual patients during the first or recurrent episodes of genital herpes simplex type 2 (HSV-2) infections. These cells were incubated with a panel of lymphocyte-specific monoclonal antibodies and examined by indirect immunofluorescence and flow cytometry. Lymphocyte proliferative responses to inactivated HSV-2 (UV-HSV-2) were also determined on repeat occasions using PBL obtained from patients with first episodes of infection. Flow cytometry analysis indicated that PBL obtained within 1 week after the onset of symptoms of first episode genital herpes exhibited significantly lower OKT 4 helper/OKT 8 suppressor T-cell ratios (1.26 +/- 0.12) than cells from either normal controls (2.44 +/- 0.3, P less than 0.01) or patients with recurrent genital HSV-2 infection (2.58 +/- 0.40, P less than 0.01). This lowered ratio was due to a decrease in OKT 4-positive helper T cells present early during initial infection (30.2 +/- 2.9, P less than 0.01 compared to recurrent disease patients or controls) and was not caused by a concomitant increase in OKT 8-positive T cells. No variation was observed during the course of infection in the proportion of total T cells as determined by EAET rosette formation or reactivity with the T-cell specific monoclonal antibody 9.6. PBL obtained from patients within 1 week after symptom onset exhibited a poor proliferative response to UV-HSV-2. Maximal proliferative responses occurred 6-9 weeks after disease onset and required the presence of OKT 4-positive T lymphocytes. The results of these experiments indicate that at different stages of disease, HSV infection is accompanied by fluctuations in the ratio of helper to suppressor T cells and alterations in antigen-specific lymphocyte proliferation. These findings suggest that variations in lymphocyte proliferative responses during the course of first episode genital herpes infection may reflect disease related variations in either the number or activity of circulating OKT 4-positive T lymphocytes.