       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).

