Variation in lymphoproliferative responses during recrudescent orofacial herpes simplex virus infections

Sixty-five patients with recrudescent orofacial herpes simplex virus (HSV) infections all had circulating HSV-specific antibody measured by ELISA and cell-mediated immunity (CMI) to HSV by in vitro lymphoproliferation. Thirteen control subjects with no history of HSV were negative for both tests. Thirty-three patients, repeatedly investigated during 6 to 38 months, had between 1 and 8 recrudescences each. Lymphoproliferative responses to HSV were low during recrudescence, rose to a peak a few weeks later and then declined to a positive background level. However, ELISA titres and lymphoproliferative responses to concanavalin A were high throughout, and peripheral blood mononuclear cell (PBMC) subset numbers measured by fluorescent flow cytometry remained within normal limits. During HSV lesions, depressed lymphoproliferation to HSV was abrogated by removal of CD8+ T cells from PBMC either by using a panning technique (nine patients) or by cell sorting (three patients). Reconstitution of the CD8-depleted population suppressed the lymphoproliferative response to HSV. Depletion of CD8+ T cells did not affect lymphoproliferation to HSV outwith recrudescence (four patients), nor lymphoproliferative responses to another antigen (PPD; five patients) during recrudescence. Thus, reduced lymphoproliferation to HSV during recrudescence may be due to HSV-specific CD8+ suppressor T lymphocyte function, rather than lack of HSV-responsive lymphocytes. This may result in depression of normal CMI responses to the virus during an asymptomatic recurrence allowing recrudescent lesions to develop.