title: Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecules and cytokines.
abstract: Human activated T cells adhere to synovial fibroblast-like cells in vitro. The present study was conducted to investigate the consequences of T cell-synovial fibroblast interactions with regard to induction of adhesion molecules and proinflammatory cytokines. A sensitive Western blot technique, polymerase chain reaction (PCR) amplification, and fluorescence-activated cell sorter (FACS) analysis were used to analyze the induction of VCAM-1 and ICAM-1 expression in T cell-synovial fibroblast cocultures. VCAM-1 and ICAM-1 expression could be induced in synovial fibroblast-like cells by 2 h. PCR amplification showed that both forms of VCAM-1 mRNA are found after the interaction of synovial fibroblasts with T cells. Up-regulation of VCAM-1 and ICAM-1 was confined to synovial fibroblasts; T cells did not express VCAM-1 or increased ICAM-1. In contrast to the T cell-synoviocyte interaction, the interaction between T cells and dermal fibroblasts resulted in the up-regulation of ICAM-1 but not VCAM-1, suggesting tissue-specific regulation of VCAM-1. The T cell-synovial fibroblast interaction also resulted in increased levels of tumor necrosis factor (TNF), interferon-gamma, and interleukin-6 in coculture supernatant. Of the neutralizing antibodies used against these cytokines, only anti-TNF could significantly inhibit VCAM-1 and ICAM-1 expression. When T cells were separated from synoviocytes by a chamber that allowed medium exchange but no cell contact, VCAM-1 and ICAM-1 failed to be up-regulated and cytokine accumulation in cocultures was drastically reduced. Our results demonstrate mutual cell activation of T cells and synoviocytes upon cell contact as shown by the release of T cell- and synoviocyte-specific cytokines and suggest a cell contact-mediated and T cell-initiated mechanism for the chronic accumulation and retention of mononuclear cells via VCAM-1/ICAM-1 by synovial fibroblasts in the rheumatoid synovium.
authors.affiliation: Institute for Inflammation and Autoimmunity, Miles Research Center, West Haven, Connecticut 06516.
authors.forename: M P
authors.initials: MP
authors.lastname: Bombara
authors.forename: D L
authors.initials: DL
authors.lastname: Webb
authors.forename: P
authors.initials: P
authors.lastname: Conrad
authors.forename: C W
authors.initials: CW
authors.lastname: Marlor
authors.forename: T
authors.initials: T
authors.lastname: Sarr
authors.forename: G E
authors.initials: GE
authors.lastname: Ranges
authors.forename: T M
authors.initials: TM
authors.lastname: Aune
authors.forename: J M
authors.initials: JM
authors.lastname: Greve
authors.forename: M L
authors.initials: ML
authors.lastname: Blue
mesh_terms: D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma