The activation pathway of CD8 positive suppressor T cells induced by human intestinal epithelial cells.
Item
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Title
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The activation pathway of CD8 positive suppressor T cells induced by human intestinal epithelial cells.
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Identifier
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AAI9405549
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identifier
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9405549
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Creator
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Li, Yin.
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Contributor
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Adviser: Lloyd Mayer
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Date
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1993
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Microbiology | Health Sciences, Immunology | Biology, Cell
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Abstract
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The immunologic hyporesponsiveness of the human gastrointestinal tract to dietary proteins has been demonstrated to be mediated by the generation of suppressor T cells. Human intestinal epithelial cells are able to function as antigen presenting cells to process and present antigens to T cells and selectively induce the activation of a CD8{dollar}\sp+{dollar} suppressor T cell subset, in a manner distinct from other conventional antigen presenting cells (i.e. macrophages). The activation of CD8{dollar}\sp+{dollar} suppressor T cells appears to be regulated by the binding of a novel CD8 ligand (non class I molecule), expressed on epithelial cells, to CD8 molecules on T cells. Co-culture of normal epithelial cells with peripheral blood T cells activates a CD8 associated src-like protein tyrosine kinase, p56{dollar}\sp{lcub}\rm lck{rcub}{dollar} and induces cellular substrate phosphorylation, including a unique 97kD protein. The upregulation of p56{dollar}\sp{lcub}\rm lck{rcub}{dollar} is found to be an early and essential event during T cell activation in this system. The increased enzymatic activity of p56{dollar}\sp{lcub}\rm lck{rcub}{dollar} can be measured within 1 minute, maintained for about 5 minutes after stimulation with epithelial cells. The selective binding to CD8 and activation of CD8-associated p56{dollar}\sp{lcub}\rm lck{rcub},{dollar} but not CD4-associated p56{dollar}\sp{lcub}\rm lck{rcub}{dollar} is demonstrated by both antibody blocking and selective stimulation of a murine transfectant expressing human CD8. The molecular weight of two putative candidate CD8 ligands expressed on epithelial cells have been identified by both western blot and {dollar}\sp{lcub}35{rcub}{dollar}S metabolic labelling assay. While binding to and stimulation through CD8 molecules are necessary, cross-linking CD8 alone with monoclonal antibody is not sufficient to drive T cell proliferation. By employing specially constructed bifunctional antibodies, T cells expressing suppressor function can be activated by the bifunctional antibody anti-CD3/CD8. Similar to epithelium mediated stimulation, anti-CD3/CD8 induced T cell activation involves protein tyrosine kinase p56{dollar}\sp{lcub}\rm lck{rcub}{dollar} activation, which can be inhibited by genestein. In contrast to cross-linking CD3 and CD8, bifunctional antibody anti-CD3/CD28 activates T cells carrying cytotoxic function. These data imply that different combinations of surface stimulation deliver unique signals to T cells and trigger specific T cell subset activation.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
