CD4+ Cell Oligoclonality in Crohn's Disease: Evidence for an Antigen-Specific Response

Gulwani‐Akolkar, Beena; Akolkar, Pradip N.; Minassian, Arax; McKinley, Matthew; Fisher, Stanley E.; Silver, Jack

doi:10.1016/0198-8859(96)00079-1

Cited by 21 publications

(13 citation statements)

References 24 publications

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“…These observations confirm our previous conclusion that CD is accompanied by repertoire changes that occur predominantly in CD4 ϩ LPL (24). These studies also reveal that although each patient is characterized by a unique pattern of repertoire differences, there are several BV segments that uniformly increase in the disease-active tissue of all seven CD patients relative to disease-inactive tissue.…”

Section: Discussionsupporting

confidence: 90%

“…This is supported by other studies demonstrating higher levels of IL-2 mRNA and an increased frequency of cells secreting IL-2 and IFN-␥ in actively inflamed CD tissue compared to sites of inactive disease (19)(20)(21)(22)(23). Finally, recent studies suggest that CD is accompanied by changes in the T cell receptor (TCR) repertoire of LPL that occurs predominantly in the CD4 ϩ population (24). Despite all of these studies, the nature of the stimulus that leads to activation of T cells in CD still remains undefined.…”

Section: Introductionsupporting

confidence: 62%

“…Previous studies from this laboratory in which the TCR repertoires of PBL and LPL within the same individual were compared had suggested that CD is accompanied by an alteration in the TCR repertoire of LPL that occurs predominantly in CD4 ϩ cells (24). To confirm this observation in a more definitive way, the TCR repertoires of LPL from both the disease-active and disease-inactive portions of the colons of seven CD patients were compared to each other.…”

Section: Resultsmentioning

confidence: 97%

“…By comparing disease-active and disease-inactive tissue within the same individual, we could eliminate the possibility that any observed differences in repertoire were caused by individual genetic differences or mode of ther- apy. Furthermore, since LPL from disease-active and diseaseinactive tissues were derived from adjacent surgical specimens, we minimized repertoire differences that might be caused by cellular compartmentalization, such as those we have previously documented for T cells from peripheral blood and the lamina propria compartment (24). This was confirmed by our comparison of LPL isolated from two adjacent segments of disease-active tissue of several CD patients, where we observed very few differences in CDR3 length profiles (data not shown) and repertoire (Table III).…”

Section: Discussionmentioning

confidence: 99%

“…Mononuclear cells from lamina propria were isolated by the method of Bull and Bookman (26), modified as previously described (24). Briefly, colonic mucosa was cut into small pieces and incubated with DTT, followed by EDTA treatment.…”

Section: Methodsmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 62%

Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

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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Repertoire analysis of memory T‐cell receptors in Japanese patients with inflammatory bowel disease

et al. 2020

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Background and Aim The T‐cell receptor (TCR) repertoire was assessed in response to various antigens and was considered to be associated with the pathogenesis of inflammatory bowel disease (IBD). Thus, we performed TCR repertoire analysis to examine the pathology of IBD from changes in the TCR repertoire of memory T cells in the intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) of patients with IBD. Methods LPMCs in the surgical specimens and PBMCs were isolated from 12 patients with IBD (5 patients with ulcerative colitis [UC] and 7 patients with Crohn's disease [CD]). PBMCs were collected from 10 healthy individuals as controls. Comprehensive TCR sequence analyses of adaptor‐ligation polymerase chain reaction (PCR) products were performed using MiSeq. Results The diversity of TCR‐α and TCR‐β in PBMCs was significantly lower in patients with IBD than that in controls ( P = 0.00084 and 0.0013, respectively). Comparisons of TCR diversity in LPMCs and PBMCs between CD and UC showed that the diversity in LPMC was not affected by diseases, whereas that in PBMCs was significantly lower in CD than in UC ( P = 0.045 and 0.049, respectively). Some TCR clones may have shown a specific increase or decrease in CD and UC, and many clones were common to both LPMCs and PBMCs in the same patients. Conclusion The diversity of TCR clones in LPMCs and PBMCs in patients with IBD was significantly lower than that of PBMCs in controls. TCR diversity in PBMCs was particularly low in patients with CD.

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Towards an understanding of the role of NOD2/CARD15 in the pathogenesis of Crohn's disease

Philpott

Viala

2004

Best Practice & Research Clinical Gastroenterology

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CD4+ Cell Oligoclonality in Crohn's Disease: Evidence for an Antigen-Specific Response

Cited by 21 publications

References 24 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.

Repertoire analysis of memory T‐cell receptors in Japanese patients with inflammatory bowel disease

Towards an understanding of the role of NOD2/CARD15 in the pathogenesis of Crohn's disease

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