Integrin alpha(1)beta(1) (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen

Intraepithelial lymphocytes (IELs) from human intestinal epithelium are mem ory CD8(+) T cells that bind to epithelial cells through human mycosal lymp hocyte (HML)-1 and to mesenchymal cells through very late activation antige n-4 (VLA-4). Their binding of extracellular matrix proteins and the mechani sm involved were tested. Activated Cr-51-labelled lymphocytes were incubate d in protein-coated microwells with various additives. After washing, the a dherent cells were detected by radioactivity. The percentages of activated IELs that bound to collagen types I and IV were 20 and 31%, respectively; f ewer bound to fibronectin or laminin. Compared to interleukin-2-activated p eripheral blood CD8(+) T lymphocytes, more IELs bound collagen IV and fewer bound fibronectin. IEL adhesion to collagen (but not fibronectin or lamini n) was up-regulated by antibody ligation of CD2 or by protein kinase C stim ulation by phorbol ester; staurosporine reduced binding, while herbimycin, phytohaemagglutinin and CD3 ligation had no effect. Antibody-blocking of in tegrin VLA-1 subunits alpha(1) (CD49a) and beta(1), (CD18) inhibited adhesi on to collagen type I by 82 +/- 6% and to type IV by 94 +/- 1% (P < 0.001), implicating VLA-I as the main collagen receptor for IELs. Cell adhesion wa s dependent on extracellular divalent cations, a characteristic event of VL A-I never before shown for IELs: manganese and magnesium ions supported bin ding in a dose-dependent manner; calcium ions inhibited their effectiveness . Therefore, IELs bind collagen through integrin alpha(1)beta(1) after prot ein kinase C activation. Adhesion is modulated by divalent cations.