Intestinal intraepithelial lymphocytes bind to colon cancer cells by HML-1 and CD11a.

Abstract

Human intraepithelial lymphocytes (IEL), predominantly CD8+ T-lymphocytes located between intestinal epithelial cells (EC), may represent the first-line immune defense against colon cancer. The mechanism by which IEL bind to the colon cancer line, DLD-1, was evaluated. A larger fraction of IEL than peripheral blood mononuclear cells bound to DLD-1 monolayers (25 +/- 16 versus 8 +/- 4% binding, P < 0.05). Binding increased when DLD-1 monolayers were incubated with interferon-gamma but not with tumor necrosis factor-alpha. Similar numbers of IEL adhered to EC tumors, HT-29 and 5637, and the non-EC tumor, A375, but fewer bound to nonmalignant smooth muscle (HISM) and fibroblast (KD) lines (P < 0.01). Binding of IEL to DLD-1 was reduced by monoclonal antibodies to HML-1 and CD11a (47 +/- 9 and 26 +/- 13% inhibition, respectively) and was completely eliminated by both combined (93 +/- 4% inhibition). Anti-HML-1 also inhibited the binding of IEL to other EC tumors but did not affect binding to non-EC tumors or fibroblasts. To conclude, the binding of IEL to EC tumors is mediated by HML-1 and CD11a [A. I. Roberts, S. M. O'Connell, and E. C. Ebert. Binding of intraepithelial lymphocytes to colon cancer cells is mediated by HML-1 and LFA-1 (abstract). Gastroenterology, 102: A685, 1992].