Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium.

Williams, William V.; Fang, Qiong; DeMarco, Deborah M.; VonFeldt, Joan M.; Zurier, Robert B.; Weiner, David B.

doi:10.1172/jci115866

Cited by 99 publications

(51 citation statements)

References 41 publications

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“…Moreover, in this study, we did not detect skewed BV17 and other BV genes that were described in Caucasian RA patients. [19][20][21][22][23] The observations have raised the possibility that in this study, overexpression of BV16 and lack of skewed BV17 and some other BV genes described in other reports may be characteristically associated with Chinese RA patients, while BV14 skewing is common to both Caucasian and Chinese patients with RA. Such discrepancies in BV gene skewing may be attributable to both genetic background (eg HLA genes) and environmental factors of geographic significance.…”

Section: Discussionsupporting

confidence: 49%

“…[19][20][21][22][23] Analysis of CDR3 of overexpressed BV genes has revealed some clonotypes that only exist in rheumatoid synovium but not peripheral T cells, suggesting T-cell clonal expansion in the affected joints in RA. [24][25][26] However, clonality and TCR BV gene usage of infiltrating T cells in RA SF or membranes are relatively heterogeneous, which complicates BV gene analysis using regular or semiquantitative PCR.…”

Section: Introductionmentioning

confidence: 99%

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Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Sun

Nie²,

et al. 2005

Genes Immun

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T-lymphocytes play an important role in rheumatoid arthritis (RA). In this study, we evaluated the hypothesis that common T-cell receptor (TCR) structural features may exist among infiltrating T cells of different RA patients, if the TCR repertoire is shaped by interaction with common self or microbial antigens in the context of susceptible HLA genes in RA. Synovial lesion tissue (ST), synovial fluid (SF) and blood specimens from RA patients and controls were analyzed for TCR V gene repertoire by real-time PCR. There was highly skewed BV14 and BV16 usage in synovial T cells of RA as opposed to those of controls, which was accompanied with a trend for correlation between skewed BV16 and DRB1*0405. Immunoscope analysis of the V-D-J region of ST-derived T cells demonstrated oligoclonal and polyclonal expansion of BV14 þ and BV16 þ T cells. Detailed characterization using specific BV and BJ primers further revealed common clonotypes combining the same BV14/BV16, BJ and CDR3 length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and CDR3 structural characteristics among synovial infiltrating T cells of RA.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Sun

Nie²,

et al. 2005

Genes Immun

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“…These observations led to the use of anti-TCR mAbs and vaccination with synthetic peptides of the CDR2 and CDR3 TCR regions; both proved beneficial in experimental allergic encephalomyelitis (33,35). Limited TCR gene rearrangements have been found in lymphocytes infiltrating brains of multiple sclerosis patients (36), synovial tissues of rheumatoid arthritis patients (37), liver of primary biliary cirrhosis (38), and in the thyroid ofthyroiditis patients (39). In multiple sclerosis plaques a dominant CDR3 sequence identical with that of TCR clones specific for myelin basic protein has been found (40).…”

Section: Discussionmentioning

confidence: 99%

Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.

et al. 1993

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“…Moreover, the selective location of different TCRBV clones in the dermis or the epidermis is also in accordance with a nonrandom tissue migration of these cells. Selective expansion of T cells in target organs has been observed in various autoimmune diseases (25)(26)(27). Part of the TCRBV profile in Omenn's syndrome might thus be attributed to an autoimmune reaction towards undetermined antigen(s).…”

Section: Cd8mentioning

confidence: 99%

Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndrome.

Rieux-Laucat¹,

Bahadoran²,

Brousse³

et al. 1998

J. Clin. Invest.

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Omenn's syndrome is an inherited human combined immunodeficiency condition characterized by the presence of a large population of activated and tissue-infiltrating T cells. Analysis of the TCRB repertoire revealed a highly restricted TCRBV usage in three patients. More strikingly, T cell clones from the three patients expressed TCRB chains with VDJ junction similarities, suggesting a common antigenic specificity. Analysis of the TCRA repertoire in one patient also revealed a restricted TCRAV usage. Finally, analysis of the TCRBV repertoire of tissue-infiltrating T cells in one patient suggested nonrandom tissue migration. These results suggest that the oligoclonal expansion of T cells observed in Omenn's syndrome could be the consequence of autoimmune proliferation generated by a profound defect in lymphocyte development. ( J. Clin. Invest. 1998. 102:312-321.)

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Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium.

Cited by 99 publications

References 41 publications

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.

Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndrome.

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