T-CELLS BOUND BY VASCULAR CELL-ADHESION MOLECULE-1 CD106 IN SYNOVIAL-FLUID IN RHEUMATOID-ARTHRITIS - INHIBITORY ROLE OF SOLUBLE VASCULAR CELL-ADHESION MOLECULE-1 IN T-CELL ACTIVATION/

Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) /CD106 have been reported in synovial fluid (SF) from patients with rh eumatoid arthritis (RA), In the present study, VCAM-1-positive lymphoc ytes were found in SF from RA patients, The data strongly suggest that sVCAM-1 might be bound to lymphocytes in SF, rsVCAM-1 in the fluid ph ase can bind to both SF lymphocytes and IL-2-dependent T cell lines wi th up-regulated expression and binding activity of VLA-4, Furthermore, proliferative responses of SF mononuclear cells (SFMC) with PHA, immo bilized anti-CD3, or anti-CD2 and PMA were inhibited to various extent s in the presence of rsVCAM-1, but only PMA-induced proliferative resp onse of PBMC from normal individuals was inhibited notably in the pres ence of rsVCAM-1, rsVCAM-1 also drastically reduced IL-2 production of Jurkat leukemic T cells possessing high affinity VLA-4 with the stimu lation of anti-CD3 and PMA, suggesting that the T cell hyporesponsiven ess induced by rsVCAM-1 might stem from impairment of IL-2 production, These results indicate that sVCAM-1 provides a negative signal to T c ell activation, probably by affecting the pathway of protein kinase C activation, Thus, binding of sVCAM-1 to SF lymphocytes might partly ex plain the anergic state of these lymphocytes.