Equivalent recognition of a varicella-zoster virus immediate early protein (IE62) and glycoprotein I by cytotoxic T lymphocytes of either CD4+ or CD8+ phenotype.

Abstract

Immunity to varicella-zoster virus (VZV), a member of the alpha-herpes virus family, exemplifies the host response to an ubiquitous human viral pathogen. In this investigation of the cytotoxic T lymphocyte (CTL) response to VZV, the depletion of CD4+ T lymphocytes made it possible to demonstrate CD8(+)-mediated cytotoxic function against autologous VZV-infected lymphoblastoid cells targets. CTL recognition of two major VZV proteins, the immediate early protein (IE62) and gp I, was demonstrated in limiting dilution cultures of T lymphocytes obtained from immune donors, stimulated with inactivated VZV Ag, and tested against lymphoblastoid cells infected with vaccinia recombinants expressing these VZV proteins. Among 11 VZV donors tested at least 20 y after primary infection, the mean precursor frequency for T lymphocytes that recognized the IE62 protein was 1:105,000 +/- 85,000 SD, with a range of 1:13,000 to 1:231,000. The mean frequency of CTL precursors specific for gp I in 11 subjects was equivalent, with a mean of 1:121,000 +/- 86,000 SD (range 1:15,000 to 1:228,000) (p = 0.68). Limiting dilution cultures were also prepared using purified CD4+ or CD8+ T lymphocyte populations recovered from PBMC by sterile fluorescence-activated cell sorting. CTL precursors that recognized the IE62 protein or gp I were derived from each of the major T lymphocyte populations by stimulation with inactivated VZV Ag; CD4+ and CD8+ CTL precursor frequencies for the IE62 protein and gp I were equivalent (p = 0.2). We conclude that antiviral CTL activity against targets expressing VZV proteins was mediated equally well by T lymphocytes of the CD4+ or CD8+ phenotype and that antiviral CTL function could be elicited in each subpopulation by exposure to non-infectious viral Ag.