Open AccessT Lymphocyte Adhesion to Human Synovial Fibroblasts. Role of Cytokines and the Interaction Between Intercellular Adhesion Molecule 1 and CD11a/CD18
Author(s) -
Krzesicki Raymond F.,
Fleming William E.,
Winterrowd Greg E.,
Hatfield Cheryl A.,
Sanders Martin E.,
Chin Jia En
Publication year - 1991
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780341007
Subject(s) - cd18 , intercellular adhesion molecule 1 , cell adhesion molecule , lymphocyte function associated antigen 1 , tumor necrosis factor alpha , adhesion , cell adhesion , microbiology and biotechnology , cd11a , proinflammatory cytokine , chemistry , intercellular adhesion molecule , icam 1 , immunology , cell–cell interaction , biology , inflammation , immune system , integrin alpha m , organic chemistry
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.