Herpes simplex virus protein targets for CD4 and CD8 lymphocyte cytotoxicity in cultured epidermal keratinocytes treated with interferon-gamma

J Infect Dis. 1996 Jan;173(1):7-17. doi: 10.1093/infdis/173.1.7.

Abstract

In early recurrent herpetic lesions, CD4 T lymphocytes are the predominant infiltrating cells, and keratinocytes expressing major histocompatibility complex (MHC) class II antigens, induced by interferon-gamma (IFN-gamma), are the major site of herpes simplex virus (HSV) replication. IFN-gamma pretreatment of human keratinocytes in vitro reduced MHC class I antigen down-regulation by HSV-1 infection and induced expression of HLA-DR that was unaltered by subsequent HSV-1 infection. Incubation of these infected keratinocytes with phosphonoacetic acid (PAA) almost completely inhibited expression of four major HSV glycoproteins, although expression of early proteins was not affected. Weak CD8 T lymphocyte cytotoxicity against IFN-gamma-stimulated, HLA-DR-expressing HSV-1-infected keratinocytes was consistently directed to the immediate early/early proteins (all 9 patients tested) but against late proteins to a lesser degree (4/9 patients). However, CD4 T lymphocyte cytotoxicity was much greater and directed predominantly against late HSV-1 glycoproteins (all 9 subjects tested) in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Down-Regulation
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Flow Cytometry
  • Herpesvirus 1, Human / physiology*
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class II / biosynthesis
  • Humans
  • Immediate-Early Proteins / biosynthesis
  • Interferon-gamma / pharmacology*
  • Keratinocytes / drug effects
  • Keratinocytes / immunology*
  • Keratinocytes / virology
  • Killer Cells, Natural / immunology
  • Phosphonoacetic Acid / pharmacology
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors / pharmacology
  • Skin / cytology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Viral Envelope Proteins / biosynthesis

Substances

  • Antiviral Agents
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immediate-Early Proteins
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • Viral Envelope Proteins
  • Interferon-gamma
  • Phosphonoacetic Acid