The Journal of Immunology, Vol 137, Issue 9 2901-2906, Copyright © 1986 by American Association of Immunologists

ARTICLES

T lymphocyte adhesion to endothelial cells: mechanisms demonstrated by anti-LFA-1 monoclonal antibodies

D Haskard, D Cavender, P Beatty, T Springer and M Ziff

Adhesion of lymphocytes to vascular endothelium is the first event in the passage of lymphocytes into a chronic inflammatory reaction. To investigate molecular mechanisms of T-EC adhesion, monoclonal antibodies (Mab) against T cell surface antigens have been tested for inhibition of binding. Baseline and phorbol ester-stimulated adhesion were strongly inhibited by either Mab 60.3 (reactive with the beta- chain of the LFA-1, OKM1, and p150,95 molecules) or by Mab TS 1/22 (specific for the alpha-chain of LFA-1). Although the increased binding of phorbol ester-stimulated lymphocytes was inhibited by anti-LFA-1 antibody, there was no increased expression of LFA-1 on phorbol ester- stimulated T cells, as determined by FACS analysis. Maximal inhibition of unstimulated and phorbol ester-stimulated T-EC adhesion was seen at Mab concentrations of 1 microgram/ml. In contrast, LPS- and IL 1- enhanced T-EC adhesion were only weakly inhibited by these antibodies. Mab 60.3 and TS 1/22 did not stain either unstimulated EC or LPS- or IL 1-stimulated EC, as measured by FACS analysis; moreover, preincubation of EC alone with these antibodies did not lead to inhibition of T-EC binding. Adhesion was not affected by Mab against the sheep erythrocyte receptor (LFA-2), a nonpolymorphic HLA class 1 framework antigen, or against LFA-3, the alpha-chain of OKM1, or the alpha-chain of p150,95. These results suggest that the mechanism of binding of lymphocytes to unstimulated endothelium differs from that to stimulated endothelium. LFA-1 appears to be an important adhesion-related molecule for binding to unstimulated endothelium. However, the increased lymphocyte adhesion to IL 1- or LPS-stimulated EC observed in these experiments appears to be relatively independent of LFA-1. The increased adhesion to stimulated EC could be due either to an increase in the avidity or the density of the EC receptor molecules ordinarily involved in unstimulated T-EC binding or to the formation of alternative receptors on the stimulated EC that are not present on unstimulated cells.

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