Augmented Numbers of HLA‐DR‐Positive T Lymphocytes in the Synovial Fluid and Synovial Tissue of Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis

Førre, Ø.; Dobloug, Jan H.; Natvig, J. B.

doi:10.1111/j.1365-3083.1982.tb00643.x

Cited by 84 publications

(32 citation statements)

References 15 publications

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“…In this study, a fraction of SF T cells from patients with oligoarticular JA were found to express activation markers [2][3][4][5]. Therefore, such cells were preferentially expanded in the presence of low-dose rIL-2 and cloned.…”

Section: Discussionmentioning

confidence: 70%

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: 70%

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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“…The SF leucocyte count in our patients ranged between 120 and 9200/ram 3 and 53.7% of the cells were PMNC. Forre et al [17] found increased CD3+ and HLA-DR+ T cells in SF of JCA patients. Venables [16] reported decreased counts of B cells and increased CD8+ cells in SF.…”

Section: Discussionmentioning

confidence: 98%

Study of pro-inflammatory (TNF-?, IL-1?, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: Correlations with clinical and laboratory parameters

1998

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Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active (n = 22) and inactive (n = 14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF-alpha and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF-alpha and IL-1alpha levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF-alpha concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF-alpha concentrations may be used as markers of disease activity.

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“…It has been suggested that recognition of arthritogenic antigen presented in the context of a limited range of major histocompatibility complex molecules by T-cell receptors (TCRs) of disease-promoting T lymphocytes results in the triggering of a pathogenic immune response. The strong association between JRA and certain major histocompatibility complex class II specificities (3)(4)(5) and the histopathology of the diseased joint (6)(7)(8) (18) and the first-strand cDNA was synthesized as described (19).…”

mentioning

confidence: 99%

Dominant T-cell-receptor beta chain variable region V beta 14+ clones in juvenile rheumatoid arthritis.

Grom

Thompson²,

Luyrink³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The characteristic histopathology and major histocompatibility complex associations in juvenile rheumatoid arthritis suggest an oligoclonal antigen-specific T-cell population may be critical to pathogenesis. To test this, we analyzed the T-cell repertoire of a polyarticular HLA-DR4+ juvenile rheumatoid arthritis patient with an aggressive form of disease that required arthrocentesis of the knee joints and early replacement of both hipjoints. A comparison ofT-cell-receptor showed that the T-cell response in the synovia was oligoclonal. Offour clones found, one was present in alljoints examined and persisted over time. This clone accounted for 67% and 74% of all V,B14+ clones sequenced in two synovial fluid samples and 75% and 40% in two synovial tissue samples. This clone was also found at a lesser frequency in peripheral blood samples. Further studies provided evidence for the presence of oligoclonauy expanded populations of T cells utilizing the V,B14

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Augmented Numbers of HLA‐DR‐Positive T Lymphocytes in the Synovial Fluid and Synovial Tissue of Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis

Cited by 84 publications

References 15 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

Study of pro-inflammatory (TNF-?, IL-1?, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: Correlations with clinical and laboratory parameters

Dominant T-cell-receptor beta chain variable region V beta 14+ clones in juvenile rheumatoid arthritis.

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