The importance of the t cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis

Panayi, G. S.; Lanchbury, Jerry S.; Kingsley, Gabrielle

doi:10.1002/art.1780350702

Cited by 436 publications

(232 citation statements)

References 42 publications

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“…There is general consensus that T lymphocytes act as initiators of joint inflammation in RA [30,31] by migrating to the affected joints, recognizing peptides deriving from processed antigens and releasing a host of cytokines [32,33]. Such cytokines, in turn, may influence the function of other cell types, such as macrophages, dendritic cells, synoviocytes and neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype

Gattorno¹,

Facchetti

Ghiotto

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe aim of the present study was to investigate the patterns of cytokine production by T cell clones raised from in vivo activated synovial fluid (SF) mononuclear cells (MNC) of five patients with oligoarticular juvenile arthritis (JA). Freshly isolated SF T cells were cultured in vitro with low dose recombinant IL-2 and subsequently cloned by limiting dilution. Sixty-four clones were obtained from the five patients studied. Fifty-nine clones were TCR a/b þ , either CD4 þ (n ¼ 43) or CD8 þ (n ¼ 15). The remaining five clones were TCR g/d þ , CD4 ¹ , CD8 ¹ . Clone immunophenotypes differed in the individual patients. Forty-four T cell clones were stimulated with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) and supernatants tested for the presence of IL-2, IL-4, IL-5 and interferon-gamma (IFN-g) by ELISA or bioassays. Cytokine mRNA accumulation was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). Most of 44 clones tested released large amounts of IFN-g irrespective of the immunophenotype. Of these, 27 were classified as Th1-type and 17 as Th0-type based upon the IFN-g/IL-4 ratio in culture supernatants. Finally, when 10 representative T cell clones were tested for pro-and anti-inflammatory cytokines, gene expression by RT-PCR, all of them were found to express the granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-a), IL-10 and transforming growth factor-beta 1 (TGF-b1) genes, and half of them IL-6 and IL-8 mRNA. In conclusion, T cell clones, that represent the progeny of in vivo activated SF T cells from oligoarticular JA patients, display heterogeneous immunophenotypes, but all share the ability to produce large amounts of IFN-g, with a predominant Th1/Th0 pattern. The expression of pro-and anti-inflammatory cytokine genes in these clones suggests that in vivo activated SF T cells modulate joint inflammation in a complex fashion.

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Section: Discussionmentioning

confidence: 99%

Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype

Gattorno¹,

Facchetti

Ghiotto

et al. 1997

Clinical and Experimental Immunology

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“…Rheumatoid arthritis (RA) is a chronic disease of unknown cause that presents a characteristic constellation of features, including synoviocyte hyperplasia, which results in pannus formation and joint destruction (15)(16)(17). The rheumatoid synovium consists of epithelial cells, which include 2 types of synovial lining cells, fibroblast-like synoviocytes (FLS) and macrophagelike synoviocytes, as well as infiltrating leukocytes, which include T cells, B cells, and dendritic cells, among others (18).…”

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confidence: 99%

MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis

Nakamachi¹,

Kawano²,

Takenokuchi³

et al. 2009

Arthritis & Rheumatism

303

209

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Objective. To elucidate the role of microRNA (miRNA) in the pathogenesis of rheumatoid arthritis (RA), we analyzed synoviocytes from RA patients for their miRNA expression.Methods. Synoviocytes derived from surgical specimens obtained from RA patients were compared with those obtained from osteoarthritis (OA) patients for their expression of a panel of 156 miRNA with quantitative stem-loop reverse transcription-polymerase chain reaction. The miRNA whose expression decreased or increased in RA synoviocytes as compared with OA synoviocytes were identified, and their target genes were predicted by computer analysis. We used an in vitro system of enhancing the expression of specific miRNA by transfection of precursors into synoviocytes, and then we performed proliferation, cell cycle, and apoptosis assays, as well as enzyme-linked immunosorbent assays for cytokine production. The effects of transfection on predicted target protein and messenger RNA (mRNA) were then examined by Western blot analysis and luciferase reporter assay.Results. We found that miR-124a levels significantly decreased in RA synoviocytes as compared with OA synoviocytes. Transfection of precursor miR-124a into RA synoviocytes significantly suppressed their proliferation and arrested the cell cycle at the G 1 phase. We identified a putative consensus site for miR-124a binding in the 3 -untranslated region of cyclin-dependent kinase 2 (CDK-2) and monocyte chemoattractant protein 1 (MCP-1) mRNA. Induction of miR-124a in RA synoviocytes significantly suppressed the production of the CDK-2 and MCP-1 proteins. Luciferase reporter assay demonstrated that miR-124a specifically suppressed the reporter activity driven by the 3 -untranslated regions of CDK-2 and MCP-1 mRNA.Conclusion. The results of this study suggest that miR-124a is a key miRNA in the posttranscriptional regulatory mechanisms of RA synoviocytes.MicroRNA (miRNA) are a well-established class of small (ϳ22 nucleotides) endogenous noncoding RNAs that influence the stability and translation of messenger RNA (mRNA) (1). Using various computational and experimental approaches, hundreds of miRNA have been identified in numerous animal species. The miRNA genes are transcribed by RNA polymerase II as primary miRNA (pri-miRNA) (2,3). The RNase III enzyme Drosha then processes the nuclear pri-miRNA, yielding a ϳ70-nucleotide molecule known as precursor miRNA (pre-miRNA) (4), which is exported from the nucleus. Maturation of the pre-miRNA into miRNA is then mediated by the cytoplasmic enzyme Dicer (5), after which the mature miRNA is loaded into the RNA-induced silencing complex (RISC)

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“…Together, these data suggest a potential role of the sex hormones and the expression of sex hormone-binding sites on macrophages and lymphocytes in the immunopathogenesis of RA as well as other autoimmune diseases (78,79).…”

Section: Discussionmentioning

confidence: 78%

Presence of estrogen‐binding sites on macrophage‐like synoviocytes and cd8+, cd29+, cd45ro+ t lymphocytes in normal and rheumatoid synovium

Cutolo

Accardo

Villaggio

et al. 1993

Arthritis & Rheumatism

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Objective. To study the presence of estrogenbinding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age-and sex-matched healthy controls.Methods. Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue sam- ples by a dextran-coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti-estrogen receptor antibody (anti-ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CDS+ T cell subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed.Results. Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor-positive cells to be the macrophage-like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells.Conclusion. It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage-like synoviocytes, functioning as antigen-processing and antigen-presenting cells, and on antigen-experienced (memory) CDS+ T lymphocytes (CD29+, CD45RO+).Females have better humoral immune responses and are more susceptible to autoimmune diseases than males. This sex-related dimorphism in immune capabilities is thought to be related to the physiologic effects of the sex hormones on the immune system (1-6). Generally, estrogens have immunostimulatory effects, whereas androgens are immunosup-

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The importance of the t cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis

Cited by 436 publications

References 42 publications

Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype

Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype

MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis

Presence of estrogen‐binding sites on macrophage‐like synoviocytes and cd8+, cd29+, cd45ro+ t lymphocytes in normal and rheumatoid synovium

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