Immunology. 1999 Aug;97(4):679-85. Unique Identifier : AIDSLINE
Intraepithelial lymphocytes (IELs) from human intestinal epithelium are
memory CD8+ T cells that bind to epithelial cells through human mycosal
lymphocyte (HML)-1 and to mesenchymal cells through very late activation
antigen-4 (VLA-4). Their binding of extracellular matrix proteins and
the mechanism involved were tested. Activated 51Cr-labelled lymphocytes
were incubated in protein-coated microwells with various additives.
After washing, the adherent cells were detected by radioactivity. The
percentages of activated IELs that bound to collagen types I and IV were
20 and 31%, respectively; fewer bound to fibronectin or laminin.
Compared to interleukin-2-activated peripheral blood CD8+ T lymphocytes,
more IELs bound collagen IV and fewer bound fibronectin. IEL adhesion to
collagen (but not fibronectin or laminin) was up-regulated by antibody
ligation of CD2 or by protein kinase C stimulation by phorbol ester;
staurosporine reduced binding, while herbimycin, phytohaemagglutinin and
CD3 ligation had no effect. Antibody-blocking of integrin VLA-1 subunits
alpha1 (CD49a) and beta1 (CD18) inhibited adhesion to collagen type I by
82+/-6% and to type IV by 94+/-1% (P<0.001), implicating VLA-1 as the
main collagen receptor for IELs. Cell adhesion was dependent on
extracellular divalent cations, a characteristic event of VLA-1 never
before shown for IELs: manganese and magnesium ions supported binding in
a dose-dependent manner; calcium ions inhibited their effectiveness.
Therefore, IELs bind collagen through integrin alpha1beta1 after protein
kinase C activation. Adhesion is modulated by divalent cations.
JOURNAL ARTICLE Cell Adhesion/IMMUNOLOGY Cell Culture
Collagen/*METABOLISM CD8-Positive T-Lymphocytes/*METABOLISM Epithelial
Cells/*IMMUNOLOGY Extracellular Matrix Proteins/METABOLISM Human
Integrins/*METABOLISM Interleukin-2/IMMUNOLOGY Intestinal
Mucosa/*IMMUNOLOGY Lymphocyte Transformation/IMMUNOLOGY Protein Kinase
C/METABOLISM Support, U.S. Gov't, P.H.S.