Regulation of effector cell functions through the ligation of lymphocyte function-associated antigen-1 and intracellular adhesion molecule-1 leads tospontaneous regression of a rat histiocytoma

Cell adhesion molecules mediate cell-to-cell interactions, thereby regulati ng effective immune response against target cells. We have investigated the intercellular cross-talk between lymphocyte function-associated antigen-1 (LFA-1) and its counter-receptor, intercellular adhesion molecule-1 (ICAM-1 ). This interaction regulates the postadhesion events leading to the regres sion of a rat histiocytoma, AK-5, which is mediated by natural killer (NK) cells through antibody-dependent cell cytotoxicity (ADCC). Repeated systemi c administration of anti-cell adhesion molecule (anti-CAM) monoclonal antib odies (MoAbs), i.e. anti-LFA-1 and anti-intracellular adhesion molecule-1 ( anti-ICAM-1), in AK-5 tumour-bearing animals enhanced tumour growth and cau sed delayed regression. The immune suppression achieved after the administr ation of these antibodies could be attributed to the diminished cytotoxic, as well as apoptotic, activity of NK cells, The MoAbs selectively reduced t he adhesion of NK cells to the tumour cells in vitro. Flow cytometric analy sis showed down-regulation of Fas-ligand expression on NK and T cells follo wing MoAb administration in vivo. Marked reduction in the lymphokine-activa ted killer (LAK) activity of NK cells was also observed after in vitro bloc king of LFA-1 and ICAM-1 molecules. In addition, continuous MoAb administra tion induced suppression of the cytokine response. These results underline the importance of ligand binding between LFA-1 and ICAM-1, which could prov ide co-stimulation for the effector-cell functions via signalling events to induce cytotoxicity, apoptosis and cytokine production, resulting in the e fficient regression of AK-5 tumour in syngeneic hosts.