Lysis of varicella zoster virus infected cells by lymphocytes from normal humans and immunosuppressed pediatric leukaemic patients.
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. We therefore developed a clinically applicable system to study responses to VZV infected cells. Fresh blood mononuclear cells (MNC) from VZV immune donors killed VZV infected fibroblasts in an 18 h 51Cr release assay. The specificity 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 seven out of nine VZV antibody positive patients in remission who were receiving maintenance treatment for acute lymphocytic leukaemia. Three of these patients had normal lymphocyte proliferative responses to VZV. Of the two patients with normal cytotoxic responses to VZV, one had reduced proliferation. It therefore appears that presence of VZV antibody, T cell proliferative responses, and cytotoxicity are independently variable. Cytotoxicity may be more susceptible to immunosuppression than either antibody or T cell proliferation.
Bowden
R A
RA
Levin
M J
MJ
Giller
R H
RH
Tubergen
D G
DG
Hayward
A R
AR
D000914:Antibodies, Viral / Q000032:analysis; D001667:Binding, Competitive; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D014645:Herpesvirus 3, Human / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008938:Mitosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II