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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).