Immunity to Herpes Simplex Virus: Virus Reactivation Modulates Lymphokine Activity

Cell-mediated immunity to herpes simplex virus (HSV) was studied in patients with recurrent disease and in seropositive controls. Supernatants from cultures of peripheral blood mononuclear cells (PBLs) obtained during recrudescence (zero to three days after onset of lesions), convalescence (four to 14 days), and quiescence (>14 days) were assayed for their ability to augment natural killer activity of normal PBLs against K562 target cells. Supernatants obtained during recrudescence, but not those obtained during convalescence, quiescence, or from seropositive controls, failed to augment natural killer activity but contained interferon and interleukin-2. Dialysis restored the ability of the supernatants to augment natural killer activity, and herpesvirus [UV-HSV-2(G)] stimulation of recrudescent PBLs in the presence of 2 x 106 M indomethacin abrogated suppression of natural killer-enhancing activity. However, similar levels of prostaglandin E were observed in supernatants of PBLs collected throughout the disease cycle from individuals with recurrent disease or from seropositive controls. The data suggest that reactivation of latent HSV is associated with the induction of a dialyzable factor(s) that interferes with interferon or interleukin-2-mediated natural killer enhancement or both. Prostaglandin E is necessary but insufficient for suppression of natural killer-enhancing activity. Recovery from herpes simplex virus (HSV) infection is associated with the development of virus-specific immune memory, and reactivation of latent HSV is followed by clonal expansion and differentiation of precursors for both regulatory and effector lymphocytes [1-8]. Despite this apparently normal sequence of immunologic events, approximately one-half of the individuals infected with HSV type 2 (HSV-2) develop clinically symptomatic recurrences [2, 3]. This observation raises major questions about the role of the immune system in recurrent disease. In this context, it has recently been shown that patients with recurrent disease do not suffer from major im