Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet.

Kutlu, Tufan; Brousse, Nicole; Rambaud, Caroline; Deist, Françoise Le; Schmitz, J; Cerf‐Bensussan, Nadine

doi:10.1136/gut.34.2.208

Cited by 165 publications

(102 citation statements)

References 22 publications

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“…Although changes in the IEL population have been associated with human IBD [32], the biologic function of this population remains elusive. TGF-g appears to directly inhibit the proliferation of inflammatory LP CD4 + proliferation via a shift in the balance between Smad7/Tbet down-regulation and Smad2/3 up-regulation, leading to a disruption of intestinal homeostasis and the subsequent development of intestinal pathology.…”

Section: Discussionmentioning

confidence: 99%

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4⁺ T cells

et al. 2004

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Intraepithelial lymphocytes (IEL) play a key role in gut homeostasis and are critical effector cells preventing the inflammatory intestinal lesions induced in mice following oral infection with Toxoplasma gondii. In this intestinal inflammatory model, CD4 + T lymphocytes from the lamina propria (LP) synergize with the infected enterocytes to secrete pro-inflammatory chemokines and cytokines. In this study, we assessed the mechanisms accounting for the ability of IEL to modulate the inflammatory activity of these cells. Adoptive transfer of IEL purified from wild-type mice, or CD154-,CD95L-or IL-10-deficient mice infected with T. gondii completely impairs the development of the lethal ileitis in recipient mice orally infected with T. gondii. Compared with unprimed IEL isolated from naive mice, the CD8 § g TCR § g subset of primed IEL, isolated from T. gondii-infected mice, secretes increased amount of TGF-g . IEL interact with the LP CD4 + T lymphocytes, down-regulate their production of inflammatory cytokines such as IFN-+ and reduce their proliferative activity. These effects are linked to the secretion of TGF-g and are correlated with a shift in the balance between Smad7/T-bet down-regulation and Smad2/Smad3 up-regulation in LP CD4 + T lymphocytes.

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Section: Discussionmentioning

confidence: 99%

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4⁺ T cells

et al. 2004

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“…Increased numbers and an increased proportion of / relative to / IEL in the small intestinal mucosa are a hallmark of coeliac disease, whether disease is active or in remission [15][16][17]. In addition, healthy first degree relatives of coeliac disease patients have increased numbers of / IEL in the small intestinal mucosa, and this correlates with whether or not those subjects express the HLA class II coeliac disease susceptibility alleles [20].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, T cells that express the / form of the TCR are abundant in the lamina propria and intraepithelial region. In addition to active coeliac disease, patients with treated coeliac disease are reported to have an increased proportion of / IEL to / IEL, and this finding has been used as a diagnostic adjunct for latent coeliac disease [15][16][17][18][19]. Furthermore, increased numbers of mucosal / T cells have been noted in otherwise healthy, first degree relatives of coeliac disease patients who carry the disease-associated HLA class II susceptibility alleles [20].…”

Section: Introductionmentioning

confidence: 99%

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Holtmeier

Rowell

Nyberg

et al. 1997

Clinical and Experimental Immunology

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SUMMARYOne of the hallmarks of coeliac disease, both active and treated, is an increased number and proportion of°/± intraepithelial T lymphocytes in the small intestinal mucosa, and an increased number of°/± T cells in the small intestinal mucosa of coeliac disease patients has been associated with the inheritance of specific HLA class II DQ alleles. Nonetheless, the contribution of genetic factors to the development of the T cell receptor (TCR) ± repertoire in coeliac disease is not known. We have assessed the contribution of genetic factors to development of the TCR ± repertoire in coeliac disease, by characterizing the junctional diversity of TCR ± transcripts expressed in the intestine and peripheral blood of a pair of monozygotic (MZ) twins concordant for coeliac disease. TCR V±1, V±2 and V±3 transcripts from small intestinal and colon biopsies, and from peripheral blood mononuclear cells, were amplified by polymerase chain reaction (PCR) and the complementarity determining region (CDR)3 domains of TCR ± transcripts were analysed by denaturing PAGE and direct nucleotide sequencing. The repertoire of TCR ± transcripts and CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins concordant for coeliac disease exhibited no overlap. The TCR ± repertoire in each twin was oligoclonal, and complexity of the junctional regions of their TCR ± transcripts was typical of the repertoire in healthy adults. Thus, genetically identical individuals with coeliac disease have distinct, non-overlapping TCR ± repertoires. Moreover, genetic factors that determine disease susceptibility do not appear to select for specific TCR ± sequences or CDR3 amino acid motifs. Keywords ±T cell receptor coeliac disease monozygotic twins T cell receptor repertoire°/

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“…38 These cells are phenotypically and functionally different from the lamina propria CD4+ gliadin specific T cells, as they contain a mixture of TCR gd+ T cells, they are not CD4+ and also at least a subgroup expresses the CD94 markers. 39,40 Several studies addressed the function of IEL in disease progression, but no definitive consensus on their role in the pathogenesis of CD has emerged, although it is clear that they might be involved in epithelial damage, a key aspect of CD, 39 via epithelial engagement of FAS via FAS-L, and thus activation of the death receptor expressed on epithelia, 41 perforin release, 42 and possible recognition of Class I-like molecules expressed by 'stressed' epithelial cells.…”

Section: Gene Therapy In Celiac Diseasementioning

confidence: 99%

“…21,22 In particular, there is a possible involvement of the IEL population. 38,39,42 These IELs are increased in number and appear to be involved in the epithelial destructive phase of CD. Importantly, they are highly sensitive to the presence of IL-15, as this cytokine promotes their activation and expansion.…”

Section: Targeting a Gt Therapy In CDmentioning

confidence: 99%

Celiac Disease: a model autoimmune disease with gene therapy applications

2003

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Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet.

Cited by 165 publications

References 22 publications

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4⁺ T cells

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4⁺ T cells

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Celiac Disease: a model autoimmune disease with gene therapy applications

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Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet.

Cited by 165 publications

References 22 publications

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4+ T cells

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4+ T cells

Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Celiac Disease: a model autoimmune disease with gene therapy applications

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Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4⁺ T cells

Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4⁺ T cells