Varicella-zoster virus-specific cytotoxic T lymphocytes (Tc): detection and frequency analysis of HLA class I-restricted Tc in human peripheral blood.
The cytotoxic T-cell (Tc) response to varicella-zoster virus (VZV) is incompletely characterized. We investigated whether VZV-specific Tc restricted by class I products of the major histocompatibility complex can be generated from the peripheral blood of VZV-immune donors. Cell lines were established from peripheral blood lymphocytes (PBL) of seropositive donors by secondary in vitro restimulation. If cell-free VZV was used as the stimulating antigen, the resulting lines were predominantly CD4+ and did not show class I-restricted cytotoxicity; when autologous infected fibroblasts were used for in vitro stimulation, the resultant lines were usually cytotoxic, although in only 4 of 11 subjects tested was this cytotoxicity HLA restricted and virus specific. PBL were also tested for Tc activity without prior restimulation; VZV-specific Tc activity was only demonstrable in the PBL of a subject convalescent following zoster but not from subjects with recent varicella infection or from normal subjects. VZV-specific Tc precursor frequencies were then determined in six selected subjects by limiting-dilution analysis. A measurable frequency was detectable in four of the six seropositive subjects, ranging from 11/10(6) T cells in an asymptomatic carrier, to 63/10(6) T cells in a subject with recent zoster. We conclude that virus-specific major histocompatibility complex class I-restricted Tc precursors may be present in the peripheral blood of normal individuals seropositive for VZV but at a frequency lower than that for other herpesviruses with nonneuronal sites of latency.
Hickling
J K
JK
MRC Clinical Immunology Research Group, Royal Postgraduate Medical School, London, United Kingdom.
Borysiewicz
L K
LK
Sissons
J G
JG
D002460:Cell Line; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006562:Herpes Zoster / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D012867:Skin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000382:microbiology*
D006680:HLA Antigens