Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes.
CD8+ cytotoxic T lymphocytes (CTL) clones with specificity for herpes simplex virus (HSV) were derived from two donors with genital HSV-2 infection. These CTL clones specifically lysed HSV-infected autologous B lymphoblastoid cells, but not HSV-infected fibroblasts. Exogenous peptide loading sensitized both cell types to lysis by an HSV-specific CTL clone of known specificity. HSV infection rendered fibroblasts refractory to peptide sensitization. HSV infection also rendered fibroblasts and keratinocytes insensitive to lysis by allospecific CD8+ CTL clones. Lysis of B lymphoblastoid cells in this system was only slightly reduced by HSV infection. Reduction of fibroblast allospecific lysis was dose and time dependent and was blocked by acyclovir, indicating the involvement of a late HSV gene product. HSV caused a reduction of fibroblast cell surface HLA class I antigen, at least in part due to reduction of synthesis of heavy chain-beta 2 microglobulin heterodimers. These results suggest that HSV-induced blockade of antigen presentation by cutaneous cells to CD8+ CTL may be a mechanism by which HSV limits or evades the immune response of the host.
Department of Medicine, University of Washington, Seattle 98195.
D M
DM
Koelle
M A
MA
Tigges
R L
RL
Burke
F W
FW
Symington
S R
SR
Riddell
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H
Abbo
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L
Corey
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis*; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004285:Dogs; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology*; D007668:Kidney; D007700:Kinetics; D018139:Simplexvirus / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014709:Vero Cells
D016827:CD8 Antigens