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 predomi nant infiltrating cells, and keratinocytes expressing major histocompa tibility complex (MHC) class II antigens, induced by interferon-gamma (IFN-gamma), are the major site of herpes simplex virus (HSV) replicat ion. IFN-gamma pretreatment of human keratinocytes in vitro reduced NM C class I antigen down-regulation by HSV-1 infection and induced expre ssion of HLA-DR that was unaltered by subsequent HSV-1 infection. Incu bation of these infected keratinocytes with phosphonoacetic acid (PAA) almost completely inhibited expression of four major HSV glycoprotein s, although expression of early proteins was not affected. Weak CD8 T lymphocyte cytotoxicity against IFN-gamma-stimulated, HLA-DR-expressin g HSV-1-infected keratinocytes was consistently directed to the immedi ate early/early proteins (all 9 patients tested) but against late prot eins to a lesser degree (4/9 patients). However, CD4 T lymphocyte cyto toxicity was much greater and directed predominantly against late HSV- 1 glycoproteins (all 9 subjects tested) in these cells.