Enhanced adherence of endothelial cells to blood mononuclear cells in HAM/TSP. Predominant role of ICAM-1.

We investigated the adhesion of blood mononuclear cells (MNC) isolated from patients with HTLV-l-associated myelopathy (HAM/TSP). MNC from HAM/TSP pat ients were significantly more adherent to activated endothelial monolayers than MNC from non-HAM/TSP (controls and HTLV-I carriers) subjects. Blocking studies demonstrated that the adhesion molecules VLA-4 (GD49d), ICAM-1 (CD 54), and L-selectin (CD62L) all contributed to increased binding. However, anti-ICAM-1 antibody was the most efficient in inhibiting binding HAM/TSP p atients MNC to activated endothelial cells. Expression on MNC of molecules involved in adhesion was also studied by flow cytometry in HAM/TSP patients , HTLV-1 carriers, and healthy control subjects after two days culture with out any mitogen. In HAM/TSP patients, L-selectin expression on CD4+ and CD8 + subsets was lower than in controls; interestingly, HAM/TSP patients had l ower percentage of CD4+ subset expressing L-selectin than HTLV-I carriers. The percentage of CD4+ and CD8+ cells expressing VLA-4 was found to be simi lar to controls in both HAM/TSP patients and HTLV-I carriers. Following two days in culture without mitogen, the percentage of T cells expressing ICAM -1 increased in HAM/TSP and carriers, but not in controls. This study provi des information regarding trans-endothelial migration of MNC across the blo od brain barrier in HAM/TSP and suggests ICAM-1 and its counterpart molecul e LAF-I are involved in massive infiltration of lymphocytes observed in the spinal cord.