T Lymphocyte Adhesion to Human Synovial Fibroblasts. Role of Cytokines and the Interaction Between Intercellular Adhesion Molecule 1 and CD11a/CD18

Abstract

We studied the adhesion of human peripheral blood T lymphocytes to human synovial fibroblasts stimulated with interferon-γ (IFNγ), tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), or combinations of these cytokines. T lymphocytes bound poorly to untreated human synovial fibroblasts. IFNγ treatment resulted in the largest increase in adhesion, followed by TNFα and IL-1β. Combinations of IFNγ + TNFα and IFNγ + IL-1β had a synergistic effect on intercellular adhesion molecule 1 (ICAM-1) expression and adhesion. The increase in cellular adhesion induced by cytokines correlated with the up-regulation of the number of cells expressing ICAM-1 and the density of antigen/cell. There was no synergistic effect on leukocyte function–associated antigen 3 (LFA-3) or on HLA class I or class II antigen expression. Adhesion was only partially inhibited by anti-ICAM-1, anti-LFA-1, or anti-CD18. These findings suggest the existence of ICAM-1-independent and CD11/CD18-independent adhesion mechanisms. Anti-LFA-3 was completely ineffective as an inhibitor of adhesion. There was no additive or synergistic advantage of using combinations of antibodies to increase the level of inhibition, i.e., anti–ICAM-1 + anti–LFA-3, anti–ICAM-1 + anti-CD18, or anti–ICAM-1 + anti–LFA-1 (CD11a). Our data indicate that proinflammatory cytokines may play a prominent role in the formation and exacerbation of synovial hyperplasia, by regulating the recruitment and retention of T lymphocytes via the up-regulation of adhesion molecules on synovial fibroblasts.