Comparative sequence analysis of the human T cell receptor ? chain in juvenile rheumatoid arthritis and juvenile spondylarthropathies: Evidence for antigenic selection of T cells in the synovium

Thompson, Susan D.; Murray, Kevin; Grom, Alexei A.; Passo, Murray H.; Choi, Edmund; Glass, David N.

doi:10.1002/1529-0131(199803)41:3<482::aid-art15>3.0.co;2-g

Cited by 37 publications

(14 citation statements)

References 43 publications

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“…This finding may be explained by the reactivity of the same T cell populations to homologous peptides of either microbial or self origin (35,36). Further analysis of these T cell populations by means of a novel method, TCC, for the identification of rare antigen-specific T cells (30), showed oligoclonality of these T cell populations with largely overlapping TCR V ␤ genes.…”

Section: Discussionmentioning

confidence: 98%

Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

Massa

Costouros

Mazzoli

et al. 2002

Arthritis & Rheumatism

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Objective. To identify self T cell epitopes associated with proinflammatory immune responses and clinically active juvenile dermatomyositis (juvenile DM). The target of our search for relevant epitopes was represented by amino acid sequences shared between human skeletal myosin and Streptococcus pyogenes M5 protein. The long-term objective of the project is to identify suitable targets for immunotherapy of the disease.Methods. We used computerized algorithms to identify putative agretopes on both the human myosin and Streptococcus M5 proteins. Direct binding assays for homolog peptides were used to confirm such predictions. Antigenicity and functional cross-reactivity were evaluated by cytotoxicity assays and by measurement of cytokine levels. Specific T cells were isolated by T cell capture, and T cell receptor (TCR) V ␤ gene usage was identified by reverse transcriptase-polymerase chain reaction.Results. We identified peptides that are targets of disease-specific cytotoxic T cell responses. T cell reactivity against the self peptides correlates with clinical signs of early, active myositis. Such reactivity is accompanied by production of proinflammatory cytokines, which may contribute to the damage. T cell crossrecognition of bacterial and human homologs was shown functionally as well as by sorting peptide-specific T cells and identifying oligoclonal and largely overlapping TCR V ␤ gene usage.Conclusion. These findings represent the first identification of a self epitope in juvenile DM, providing a potential candidate for antigen-specific immune therapy.

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Section: Discussionmentioning

confidence: 98%

Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

Massa

Costouros

Mazzoli

et al. 2002

Arthritis & Rheumatism

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“…A similar sequence of events could take place in the synovia of children with JIA. In fact, as previously reported [15], the evaluation of the molecular organization of the TCR revealed that T cells proliferating in children with JIA show a preferential usage of definite TCR gene regions, indicating an ordered immune response in which a specific TCR has been triggered and CXCR3 expression is induced [16]. …”

Section: Discussionmentioning

confidence: 59%

CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis

et al. 2005

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The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional migration of activated T cells, i.e. IFNγ-inducible protein 10 (CXCL10) and its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that synovial macrophages, epithelial cells, and endothelial cells bear the chemokine. By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed at high density by virtually all T lymphocytes isolated from synovial fluid (SF) and infiltrating the synovial membrane. Particularly strongly stained CXCR3 + T cells can be observed close to the luminal space and in the perivascular area. Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3 are significantly higher in JIA patients than in controls. T cells purified from SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF exerts significant chemotactic activity on the CXCR3 + T-cell line, and this activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody. Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in the pathophysiology of JIA-associated inflammatory processes, regulating both the activation of T cells and their recruitment into the inflamed synovium.

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“…(52) Synovial fluid samples from patients with different JIA subtypes show markedly different CD4 / CD8 ratios, (53) proportions of activated CD4 and CD8 T cells, (53) degrees of clonal expansion, (54) associated HLA-DR B1 loci, and involvement of Vβ families among the highly oligoclonally expanded T cells. (55) These findings suggest that different autoantigens may be involved in different JIA subtypes. Yao et al reported mutation of the RANTES gene promoter in patients with JIA and this mutation was associated with increased RANTES secretion and synovial membrane inflammation.…”

Section: Pathogenesismentioning

confidence: 87%

New advances in juvenile idiopathic arthritis

Huang¹

2012

Biomed J

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Comparative sequence analysis of the human T cell receptor ? chain in juvenile rheumatoid arthritis and juvenile spondylarthropathies: Evidence for antigenic selection of T cells in the synovium

Cited by 37 publications

References 43 publications

Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis

New advances in juvenile idiopathic arthritis

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