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KMID : 1161520040080020125
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Animal Cells and Systems
2004 Volume.8 No. 2 p.125 ~ p.133
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TNFβ induces cytotoxicity of antibody-activated CD4+ T-lymphocytes against herpes virus-infected target cells
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Choi Sang-Hoon
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Abstract
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We have extended our previous work that cross?linking CD4 molecules using specific MAb induced antigen nonspecific, MHC unrestricted killing of virally infected target cells by CD4+ T 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 bisindolylamaleimide, a protein kinase C (PKC) 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?linking of CD4 molecules. The CD4 cross?linking failed to induce effector cell proliferation or the transcription of TNFp. Upregulation of TNFp was induced by incubating the antibody activated effector cells with BHV?1 infected D17 target cells for 10 h. Anti?TNFp antibody partially abolished (13?44%) the direct effector cell?mediated antiviral cytotoxicity. However, this antibody neutralized 70 to 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 and target cell ratio. These results support the hypothesis that increased p56 lck 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 known to participate in target cell killing were produced. A better understanding of the killing activity displayed by CD4+ T lymphocytes following surface receptor cross?linking will provide insight into the mechanisms of cytotoxic activity directed toward virally?infected cells.
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KEYWORD
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p56lck, Signal transduction, Cross-linking, In vitro kinase assay
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