T cell antigen receptor V gene usage. Increases in V beta 8+ T cells in Crohn's disease.

Posnett, David N.; Schmelkin, I; Burton, Daniel A.; August, A; McGrath, Helen; Mayer, L F

doi:10.1172/jci114634

Cited by 112 publications

(52 citation statements)

References 33 publications

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“…Various hypotheses have been proposed to explain the etiology and pathogenesis of CD, ranging from exposure to an infective agent to aberrant T cell regulation (2)(3)(4)(5)(6)(7)(8)(9). Despite this lack of basic knowledge regarding the initiating event in CD, there is reason to believe that immunological mechanisms may explain the chronicity and relapse of CD (10,11).…”

Section: Introductionmentioning

confidence: 99%

Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.

Gulwani‐Akolkar¹,

Akolkar²,

Minassian³

et al. 1996

J. Clin. Invest.

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To identify disease-specific T cell changes that occur in Crohn's disease (CD), the T cell receptor BV repertoires of lamina propria lymphocytes (LPL) isolated from both the inflamed and "disease-inactive" colons of seven CD patients were compared by the quantitative PCR and DNA sequence analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon from the same individual were very different. Furthermore, nearly all of the differences occurred in CD4 ϩ LPL, with very few differences in the CD8 ϩ population of LPL. Although the pattern of BV segments that was increased in disease-active tissue relative to disease-inactive tissue was different for all seven CD patients, there were several BV segments that increased uniformly in the disease-active tissue of all seven individuals. CDR3 length analysis and DNA sequencing of these BV segments revealed that in six of the seven CD patients there was a striking degree of oligoclonality that was absent from disease-inactive tissue of the same individual. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4 ϩ T cells to specific antigens.

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Section: Introductionmentioning

confidence: 99%

Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.

Gulwani‐Akolkar¹,

Akolkar²,

Minassian³

et al. 1996

J. Clin. Invest.

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“…21,34,35 Interestingly, expansion of Vb8 T cells has been identified in Crohn's disease, suggesting that this disorder is characterized by similar immunopathogenic processes as well as histopathology compared with sarcoidosis. 36 The existence of pathogenic T cells within the Vb8 T-cell subset in sarcoidosis is suggested by observations that individuals treated with corticosteroids or who underwent spontaneous recovery had reductions in the proportions of Vb8 T cells in the biased lung or blood T-cell compartment. It is conceivable that chronic granulomatous inflammation in sarcoidosis is determined at the tissue level by involvement of oligoclonal populations of pathogenic Vb-specific T cells.…”

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confidence: 99%

Limited heterogeneity of biased T‐cell receptor Vβ gene usage in lung but not blood T cells in active pulmonary sarcoidosis

1996

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Sarcoidosis is a multisystem disorder characterized by non‐caseating granulomas and the accumulation of CD4+ T cells in involved tissues such as the lung. To evaluate the diversity of the CD4+ T‐cell repertoire in this disorder, a detailed clonal analysis was performed in five individuals with active sarcoidosis who demonstrated preferential accumulation of T cells expressing the T‐cell receptor variable gene family Vβ8 in either the lung or blood. In three individuals, analysis of unselected samples of nucleotide sequences derived from Vβ8+ lung T cells demonstrated degrees of clonality ranging from 11% to 46%, indicating the expansion of limited numbers of Vβ8+ T‐cell clones in the lung. Analysis of the corresponding deduced amino acid sequences demonstrated common VDJ junctional amino acid residues in the dominant Vβ8+ T‐cell clones derived from two oligoclonal Vβ8+ lung T‐cell populations, consistent with an antigen‐specific T‐cell response. In contrast, analysis of Vβ8+ CD4+ T cells from the blood of an individual with a marked bias for peripheral blood Vβ8+ T cells demonstrated no evidence of oligoclonality, suggesting that the stimulus for circulating biased Vβ‐specific T cells in sarcoidosis may derive from a different, perhaps superantigenic, origin. Clinical improvement in the disease either in response to treatment with corticosteroids or as a result of spontaneous resolution was associated with a decrease in the proportion of Vβ8‐specific T cells in the biased lung and/or blood T‐cell compartments. Together, these observations are consistent with a role for this T‐cell subset in the clinical manifestations of active granulomatous disease.

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“…of extent, duration and stage of disease when the T cell population had been studied. This fact could explain contradictory results obtained by others [10,11].…”

Section: Discussionmentioning

confidence: 75%

Crohn’s disease (CD) patients suffering from peripheral arthritis or ankylosing spondylitis reveal restricted T cell receptor Vβ regions in different temporal phases of disease

Lügering

Kucharzik

Fisahn

et al. 1996

Clinical and Experimental Immunology

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SUMMARYLittle is known about the mechanisms triggering and controlling both the development and perpetuation of extraintestinal complications in CD. The aim of the present study was to test the hypothesis that the T cell immune response in CD patients with joint complications may be altered when compared with patients without extraintestinal manifestations. We used a semiquantitative polymerase chain reaction assay to analyse the T cell antigen receptor repertoire in peripheral blood T cells from eight CD patients suffering from peripheral arthritis and ankylosing spondylitis, 12 CD patients without extraintestinal manifestations, and from seven non-CD patients with ankylosing spondylitis showing typical changes on joint radiographs. Being concerned that different patterns may be seen in different phases of the inflammatory disease process, we have also taken care to analyse sequential samples at various time points of the disease. Expression of all 22 V¯genes was found in each healthy control and in each CD patient without extraintestinal manifestations and showed no major variation over time. Southern hybridization analysis of amplified products revealed a highly restricted V¯repertoire in all CD patients suffering from peripheral arthritis and ankylosing spondylitis. In contrast, non-CD patients with ankylosing spondylitis without signs or symptoms of gastrointestinal problems demonstrated the presence of the entire V¯repertoire. Our longitudinal studies confirmed variable V¯usage over time, as certain transcripts were found only in distinct temporal phases of disease. Our data are not directly suggestive of a common superantigen model of CD, but instead emphasize a specific decrease in signals throughout the T cell receptor V¯repertoire in CD patients suffering from joint complications.

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T cell antigen receptor V gene usage. Increases in V beta 8+ T cells in Crohn's disease.

Abstract: Crohn's disease represents part of a spectrum of inflammatory bowel diseases characterized by immune regulatory defects and genetic predisposition. T

Cited by 112 publications

References 33 publications

Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.

Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.

Limited heterogeneity of biased T‐cell receptor Vβ gene usage in lung but not blood T cells in active pulmonary sarcoidosis

Crohn’s disease (CD) patients suffering from peripheral arthritis or ankylosing spondylitis reveal restricted T cell receptor Vβ regions in different temporal phases of disease

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