Herpes simplex virus protein targets for CD4 and CD8 lymphocyte cytotoxicity in cultured epidermal keratinocytes treated with interferon-gamma.
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.
Mikloska
Z
Z
Virology Department, Westmead Hospital, Australia.
Kesson
A M
AM
Penfold
M E
ME
Cunningham
A L
AL
D000998:Antiviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000096:biosynthesis
D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017874:Immediate-Early Proteins; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D014759:Viral Envelope Proteins; D007371:Interferon-gamma; D010746:Phosphonoacetic Acid