title: Tumor necrosis factor beta is a major source of antibody-activated effector cells in the killing of virally infected target cells.
abstract: We have extended our previous work on cross-linking CD4 molecules using specific monoclonal-antibody-induced antigen-nonspecific major-histocompatibility-complex unrestricted killing by CD4+ T cells of virally infected target cells. The killing activity of antibody-activated CD4+ T cells was completely blocked by herbimycin A, a protein tyrosine kinase (PTK) inhibitor, but not by bisindolylmaleimide, a protein kinase C inhibitor. Herbimycin-A-treated human or bovine peripheral blood CD4+ T cells lacked PTK activity and failed to kill virally infected target cells even after cross-killing of CD4 molecules. The cross-linking of CD4 molecules failed to induce effector cell proliferation or the transcription of TNF-beta. The upregulation of TNF-beta was induced by incubating antibody-activated effector cells with bovine herpesvirus type 1 (BHV-1)-infected D17 target cells for 10 h. Anti-TNF-beta antibody partially abolished (13-44%) direct effector-cell-mediated antiviral cytotoxicity. However, this antibody neutralized 70-100% of antiviral activity of effector and target cell culture supernatants against BHV-1-infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on the effector:target cell ratio. These results support the hypothesis that increased p56lck enzyme activity in effector cells transduces a signal critical for effector cell recognition of viral glycoproteins expressed on the target cells. Following target cell recognition, lytic cytokines were produced that are known to participate in target cell killing. A better understanding of the killing activity displayed by CD4+ T lymphocytes following surface receptor cross-linking activity displayed by CD4+ T lymphocytes following surface receptor cross-linking will give insight into the mechanisms of cytotoxic activity directed toward virally infected cells.
authors.affiliation: Department of Fish Pathology, College of Ocean Science & Technology, Kunsan National University, Chonbuk, Korea. shchoi@ks.kunsan.ac.kr
authors.forename: S H
authors.initials: SH
authors.lastname: Choi
authors.forename: C W
authors.initials: CW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000998:Antiviral Agents / Q000276:immunology; D016227:Benzoquinones; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology*; D008301:Maleimides / Q000494:pharmacology; D009500:Neutralization Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D016227:Benzoquinones; D015704:CD4 Antigens; D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007211:Indoles; D047029:Lactams, Macrocyclic; D008233:Lymphotoxin-alpha; D008301:Maleimides; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011493:Protein Kinase C; C088060:bisindolylmaleimide