title: Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1).
abstract: The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T cells, is a typical histopathological feature associated with rheumatoid arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated by a number of molecules in the endothelium that are induced in response to a series of inflammatory mediators. In this study, we have investigated the adhesion of synovial T cells from RA patients to two endothelial ligands: endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to function as a vascular addressin for T cells, and vascular cell adhesion molecule-1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that synovial T cells isolated from both SM and synovial fluid (SF), bearing an activated and memory phenotype, displayed an enhanced capacity to interact with these two endothelial molecules as compared with T cells from peripheral blood (PB) either of the same RA patients or healthy donors. A further enhancement of VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when already in vivo-activated synovial T cells were stimulated in vitro with phorbol esters, suggesting the existence of several cellular affinity levels for both very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells from RA patients exhibited strong proliferative responses when they were cultured with either fibronectin or VCAM-1 in combination with submitogenic doses of anti-CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes together with their proliferation in response to the interaction with VCAM-1 and fibronectin may represent important mechanisms in the regulation of T cell penetration and persistence in the chronically inflamed SM of RA.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
authors.forename: A A
authors.initials: AA
authors.lastname: Postigo
authors.forename: R
authors.initials: R
authors.lastname: Garcia-Vicuña
authors.forename: F
authors.initials: F
authors.lastname: Diaz-Gonzalez
authors.forename: A G
authors.initials: AG
authors.lastname: Arroyo
authors.forename: M O
authors.initials: MO
authors.lastname: De Landázuri
authors.forename: G
authors.initials: G
authors.lastname: Chi-Rosso
authors.forename: R R
authors.initials: RR
authors.lastname: Lobb
authors.forename: A
authors.initials: A
authors.lastname: Laffon
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D016029:Receptors, Very Late Antigen / Q000032:analysis; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology*; D019010:Vascular Cell Adhesion Molecule-1; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015815:Cell Adhesion Molecules; D003094:Collagen; D019040:E-Selectin; D005353:Fibronectins; D006649:Histocompatibility Antigens; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D000099192:CD69 Antigens