LYSIS OF VARICELLA ZOSTER VIRUS-INFECTED CELLS BY LYMPHOCYTES FROM NORMAL HUMANS AND IMMUNOSUPPRESSED PEDIATRIC LEUKEMIC PATIENTS

Abstract

Varicella zoster virus (VZV) is an important cause of morbidity and mortality in immunosuppressed children but little is known of the cellular mechanisms of VZV immunity. Therefore, a clinically applicable system to study response to VZV infected cells was developed. Fresh blood mononuclear cells from VZV immune donors killed VZV infected fibroblasts in an 18 h 51Cr release assay. The speficicity for virus was confirmed by cold target inhibition. An enhancing role for HLA matching was demonstrated using targets mismatched for HLA, and blocking by antibodies to HLA framework and T cell subsets. Cytotoxicity was not blocked with anti-Ia or anti-VZV antibodies. Killing of VZV infected target cells was reduced in 7 of 9 VZV antibody positive patients in remission who were receiving maintenance treatment for acute lymphocytic leukemia. Three of these patients had normal lymphocyte proliferative responses to VZV. Of the 2 patients with normal cytotoxic responses to VZV, 1 had reduced proliferation. VZV antibody, T cell proliferative responses, and cytotoxicity thus appear to be independently variable. Cytotoxicity may be more susceptible to immunosuppression than either antibody or T cell proliferation.