INTERCELLULAR-ADHESION MOLECULES (ICAM)-1 ICAM-2 AND ICAM-3 FUNCTION AS COUNTER-RECEPTORS FOR LYMPHOCYTE FUNCTION-ASSOCIATED MOLECULE-1 IN HUMAN IMMUNODEFICIENCY VIRUS-MEDIATED SYNCYTIA FORMATION

It has been previously demonstrated that lymphocyte function-associate d molecule 1 (LFA-1) plays a major role in human immunodeficiency viru s (HIV)-mediated syncytia formation. In the present study we investiga ted the involvement of intercellular adhesion molecule-1 (ICAM-1), ICA M-2 and ICAM-3 in the process. The ability of monoclonal antibodies (m Ab) directed against ICAM-1, ICAM-2 and ICAM-3 to block syncytia was a nalyzed either in phytohemagglutinin (PHA)-activated lymphocytes infec ted in vitro with primary or laboratory strains of HIV or by coculturi ng a T cell line stably expressing HIV envelope with PHA-activated lym phocytes. Complete inhibition of syncytia formation was observed only by the simultaneous addition to the cell cultures of all (i.e. anti-IC AM-1, anti-ICAM-2 and anti-ICAM-3) mAb. These results indicate that th e interaction between LFA-1 and ICAM is a critical step in HIV-mediate d syncytia formation, and that ICAM-1, ICAM-2 and ICAM-3 are the recep tor molecules for the LFA-1-dependent syncytia formation.