CD4(+) cytotoxic T-lymphocyte activity against macrophages pulsed with bovine herpesvirus 1 polypeptides.
Bovine herpesvirus 1 (BHV-1) induces immune suppression, but the mechanisms for suppression are not well identified. We examined the induction and activity of BHV-1-specific cytolytic CD4(+) T lymphocytes (CTL) by stimulating peripheral blood mononuclear cells (PBMC) of cattle immunized with attenuated live BHV-1. Cytolytic effector cells were primarily CD4(+) T lymphocytes and lysed autologous, but not allogeneic, macrophages infected with BHV-1 or pulsed with BHV-1 polypeptides. Apoptosis of BHV-1-expressing target cells was observed in CD4(+) CTL assays by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) analysis. To determine if apoptosis was mediated by a perforin- or Fas-mediated pathway, EGTA, a known selective inhibitor of the perforin pathway, was used. EGTA did not inhibit CD4(+)-T-cell-mediated cytotoxic activity, but it did limit the NK cell cytotoxicity of virus infected cells. These findings support the concept that CD4(+) CTL lyse macrophages pulsed with BHV-1 polypeptides through a Fas-mediated lytic pathway by inducing apoptosis in the target cells. The prominent cytotoxicity mediated by CD4(+) CTL suggests a mechanism of selective removal of viral antigen-associated antigen-presenting cells.
Wang
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Department of Animal Health and Biomedical Science, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
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D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004533:Egtazic Acid; D007242:Herpesvirus 1, Bovine / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008274:Magnesium
D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; D004533:Egtazic Acid; D008274:Magnesium