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- Document 0374
- DOCN M9610374
- TI Human intestinal epithelial cell-induced CD8+ T cell activation is
- mediated through CD8 and the activation of CD8-associated p56lck.
- DT 9601
- AU Li Y; Yio XY; Mayer L; Division of Clinical Immunology, Mount Sinai
- Medical Center, New; York 10029, USA.
- SO J Exp Med. 1995 Oct 1;182(4):1079-88. Unique Identifier : AIDSLINE
- MED/96018807
- AB The activation of CD8+ suppressor T cells by normal intestinal
- epithelial cells in antigen-specific or allogeneic mixed cell culture
- systems has significant implications for the regulation of mucosal
- immune responses. In this study, we found that the capacity of
- epithelial cells to induce CD8+ suppressor T cell activation appeared to
- be linked to the binding of CD8 molecules on the T cell surface. This
- appears to be mediated by a non-class I molecule expressed on the
- epithelial cell surface, which binds to CD8 and results in the
- activation of the CD8-associated src-like tyrosine kinase, p56lck.
- Epithelial cell-stimulated p56lck activation is an early event (in
- contrast to monocytes) and is essential for T cell activation, since
- proliferation could be completely abrogated by pretreatment of T cells
- with genestein or herbamycin, both of which are protein tyrosine kinase
- inhibitors. Pretreatment of T cells with anti-CD8 or of intestinal
- epithelial cells with an anti-epithelial cell mAb B9 inhibited p56lck
- activation and further confirmed that CD8 on the T cell and a CD8 ligand
- on the epithelial cell were involved in this T cell activation event.
- The specificity of this reaction was confirmed in experiments in which
- murine transfectants 3G4 and 3G8, expressing CD4 or CD8, respectively,
- were used. Coculture of 3G8 with epithelial cells but not with monocytes
- activated p56lck in this cell line, whereas p56lck was preferentially
- activated in 3G4 cells when monocytes were used as the stimulator cells.
- Although stimulation through CD8- and CD8-associated p56lck was
- important for epithelial cell-induced T cell activation, T cell
- proliferation could not be induced by cross-linking CD8 alone with
- monoclonal antibody anti-CD8. These data suggest that a second signal,
- possibly through the T cell antigen receptor since activation of the T
- cell receptor-associated kinase fyn was also seen, is required for
- epithelial cell-driven T cell proliferation.
- DE src-Family Kinases/*METABOLISM Antigens, CD4/METABOLISM Antigens,
- CD8/*METABOLISM Cell Adhesion Cell Communication CD8-Positive
- T-Lymphocytes/*IMMUNOLOGY Enzyme Inhibitors
- Epithelium/CYTOLOGY/IMMUNOLOGY Human Intestines/CYTOLOGY/*IMMUNOLOGY
- Isoflavones/PHARMACOLOGY *Lymphocyte Transformation
- Monocytes/IMMUNOLOGY Protein-Tyrosine Kinase/ANTAGONISTS & INHIB
- Quinones/PHARMACOLOGY Signal Transduction Support, U.S. Gov't, P.H.S.
- JOURNAL ARTICLE
-
- SOURCE: National Library of Medicine. NOTICE: This material may be
- protected by Copyright Law (Title 17, U.S.Code).
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-