Phenotype, Cytotoxic, and Helper Functions of T Cells from Varicella Zoster Virus Stimulated Cultures of Human Lymphocytes

Abstract

Blood mononuclear cells (MNC) were stimulated with VZV in the form of live cell-associated virus, glutaraldehyde-fixed VZV-infected fibroblasts or an extracted VZV antigen. After 7 days of culture with live virus, IL2 receptors (IL2R) were found on CD4 and CD8 cells while cultures stimulated with fixed or extracted antigen had IL2R only on CD4 cells. Clones derived by limiting dilution from these cultures were tested for specificity by cytotoxicity to autologous VZV-superinfected B lymphoblasts, and by proliferation in the presence of antigen and antigen presenting cells. The CD8+ clones were not VZV specific in tests of cytotoxicity or proliferation. 50% of the CD4+ clones with specificity for VZV also proliferated in cultures stimulated with individual VZV glycoproteins gp I, II or III. Included amongst these were clones cytotoxic for lymphoblast targets prepared with live VZV. Most of the VZV-specific T cell clones which failed to lyse targets prepared with live VZV lysed targets prepared with heat killed VZV. Target cells were susceptible to lysis after VZV antigens were no longer demonstrable on the cell surface by immunofluorescence and monoclonal antibodies to VZV glycoproteins failed to block cytotoxicity. 5 of 8 VZV-specific CD4+ clones provided antigen-specific help to B cells for IgG antibody production. The data are consistent with the view that CD4+ T cells respond to processed VZV antigen fragments, and that these fragments include epitopes present on gp I, gp II and gp III. Additionally, some the cloned progeny of VZV specific T cells were bifunctional (expressing cytotoxicity and help for B cells) in tissue culture.