Abnormal intestinal intraepithelial lymphocytes in refractory sprue

Cellier, Christophe; Patey, Natacha; Mauvieux, Laurent; Jabrì, Bana; Delabesse, Éric; Cervoni, Jean–Paul; Burtin, Marie–Laure; Guy‐Grand, Delphine; Bouhnik, Yoram; Modigliani, R; Barbier, J; Macintyre, Elisabeth; Brousse, Nicole; Cerf‐Bensussan, Nadine

doi:10.1016/s0016-5085(98)70530-x

Cited by 369 publications

(261 citation statements)

References 37 publications

Supporting

Mentioning

230

Contrasting

Unclassified

Order By: Relevance

“…The latter was further subclassified as primary or secondary, based on the absence or presence of previous response to gluten-free diet, and as type I or type II, based on the presence of a polyclonal or clonal population of intraepithelial lymphocytes. [20][21][22] Cases where the underlying etiology could not be ascertained were designated as unclassified sprue. This study was approved by our Institutional Review Board.…”

Section: Clinical Datamentioning

confidence: 99%

Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients

et al. 2010

View full text Add to dashboard Cite

Collagenous sprue is associated with high morbidity; however, the etiology of this disorder is unclear. Data regarding the pathological and clinical manifestations of patients with collagenous sprue are also limited. We, thus, undertook this study to gain insight into the etiology, disease manifestations and outcomes of collagenous sprue. We searched our departmental database (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) to identify cases of collagenous sprue and to obtain clinical and laboratory data. Small bowel histology, including thickness of subepithelial collagen, intra-epithelial lymphocyte phenotype and results of T-cell clonality assays were evaluated. Nineteen patients (15 women, 4 men, age 22-80 years, mean 57 years) were identified.

show abstract

Section: Clinical Datamentioning

confidence: 99%

Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Ils se rattachent à la lignée T par l'expression intracellulaire de la chaîne CD3ε et des réarran-gements de la chaîne γ du récepteur T. Leur aspect cytologique est normal, mais leur diffusion à l'ensemble du tube digestif et parfois au sang, et le caractère clonal des réarrangements Tγ suggèrent qu'il s'agit d'une population maligne ou pré-maligne. Cette hypothèse est renforcée par l'apparition dans 15 % des cas d'un lymphome T invasif dont la parenté avec la population clonale intra-épithéliale a été démontrée dans deux cas [44,45]. Ces données confirment la modification profonde de l'homéostasie des LIE au cours de la maladie coeliaque.…”

Section: Origine De Deux Complications Malignes De La Maladie Coeliaqunclassified

La maladie cœliaque : une maladie auto-immune induite par un antigène alimentaire

Cerf‐Bensussan

Jabrì

2001

Med Sci (Paris)

Self Cite

View full text Add to dashboard Cite

L a maladie coeliaque (MC) est une entéropathie induite par les prolamines du blé (gluten) et les protéines apparentées du seigle et de l'orge. La maladie coeliaque est une maladie chronique multifactorielle impliquant des facteurs environnementaux et génétiques. Elle s'apparente moins aux allergies alimentaires qu'aux maladies auto-immunes, auxquelles elle est fréquemment associée. Néanmoins, son expression strictement dépendante d'une expo- 1129La maladie coeliaque : une maladie auto-immune induite par un antigène alimentaire La maladie coeliaque est une entéropathie auto-immune induite par un antigène alimentaire, la gliadine, chez des sujets génétiquement prédisposés. Un schéma pathogé-nique intégrant la liaison génétique aux molécules HLA et l'enzyme cible des auto-anticorps, la transglutaminase, fait jouer un rôle central aux lymphocytes T CD4 + du chorion qui répondent à certains peptides de la gliadine présentés par les molécules HLA-DQ2/8 après désamidation par la transglutaminase. La production des auto-anticorps serait secondaire à la reconnaissance par le système immunitaire de la transglutaminase complexée à la gliadine. Le méca-nisme de l'hyperplasie lymphoïde intra-épithéliale, caracté-ristique de la maladie et à l'origine de complications malignes, n'est pas élucidé. Elle pourrait être déclenchée par un peptide toxique de la gliadine distinct des peptides stimulant les lymphocytes T CD4 + , et être secondaire à l'activation de récepteurs de l'immunité innée sur les lymphocytes intra-épithéliaux et à la production de cytokines par les entérocytes modifiés par l'inflammation ou le stress. La poursuite du démembrement des facteurs génétiques et environnementaux s'avère nécessaire pour élucider les mécanismes enclenchant la réaction immune anormale à la gliadine, comprendre la très grande hétérogénéité clinique et histologique de la maladie et peut-être à terme proposer une alternative au régime sans gluten très contraignant. médecine/sciences 2001 ; 17 : 1129-38 m/s n°11, vol. 17, novembre 2001 Nadine Cerf-Bensussan Bana JabriArticle disponible sur le site

show abstract

“…Although most patients with CD improve on a gluten-free diet, a small fraction (2-5%) of patients with adult-onset CD do not and continue to experience symptoms caused by chronic inflammation of the upper small intestine. Many of these patients suffer from RCDII, characterized by an expanded lineage-negative (Lin − ) innate intraepithelial lymphocyte (IEL) population in the duodenum (2,3). Even though these Lin − innate IELs (hereinafter Lin − IELs) are defined by the absence of surface lineage markers, including several T-cell markers (CD3, CD4, CD8, CD14, CD19, and CD56), they do express intracellular CD3 (icCD3e) and usually have incomplete or out-of-frame T-cell receptor (TCR) rearrangements, suggesting that they derive from early T-cell and/or natural killer (NK)-cell precursors (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

“…Many of these patients suffer from RCDII, characterized by an expanded lineage-negative (Lin − ) innate intraepithelial lymphocyte (IEL) population in the duodenum (2,3). Even though these Lin − innate IELs (hereinafter Lin − IELs) are defined by the absence of surface lineage markers, including several T-cell markers (CD3, CD4, CD8, CD14, CD19, and CD56), they do express intracellular CD3 (icCD3e) and usually have incomplete or out-of-frame T-cell receptor (TCR) rearrangements, suggesting that they derive from early T-cell and/or natural killer (NK)-cell precursors (2)(3)(4)(5)(6). Thus, the diagnosis of RCDII is based on the detection of icCD3e + Lin − IELs (also known as aberrant IELs) by flow cytometry (7), immunohistochemistry (8), and/or PCR-based detection of clonal TCR γ-locus (TRG) rearrangements (5).…”

mentioning

confidence: 99%

CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes

Kooy–Winkelaar

Bouwer

Janssen

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin − IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin − IELs develop into a lymphoma for which no effective treatment is available. Current evidence indicates that the survival and expansion of these malignant Lin − IELs is driven by epithelial cell-derived IL-15. Like CD, RCDII is strongly associated with HLA-DQ2, suggesting the involvement of HLA-DQ2-restricted gluten-specific CD4 + T cells. We now show that gluten-specific CD4 + T cells isolated from CD duodenal biopsy specimens produce cytokines able to trigger proliferation of malignant Lin − IEL lines as powerfully as IL-15. Furthermore, we identify TNF, IL-2, and IL-21 as CD4 + T-cell cytokines that synergistically mediate this effect. Like IL-15, these cytokines were found to increase the phosphorylation of STAT5 and Akt and transcription of antiapoptotic mediator bcl-x L . Several small-molecule inhibitors targeting the JAK/STAT pathway blocked proliferation elicited by IL-2 and IL-15, but only an inhibitor targeting the PI3K/Akt/mTOR pathway blocked proliferation induced by IL-15 as well as the CD4 + T-cell cytokines. Confirming and extending these findings, TNF, IL-2, and IL-21 also synergistically triggered the proliferation of freshly isolated Lin − IELs and CD3 − CD56 + IELs (NK-IELs) from RCDII as well as non-RCDII duodenal biopsy specimens. These data provide evidence implicating CD4 + T-cell cytokines in the pathogenesis of RCDII. More broadly, they suggest that adaptive immune responses can contribute to innate IEL activation during mucosal inflammation.celiac disease | refractory celiac disease | enteropathy-associated T-cell lymphoma | small-molecule inhibitor | intraepithelial lymphocyte

show abstract

Abnormal intestinal intraepithelial lymphocytes in refractory sprue

Cited by 369 publications

References 37 publications

Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients

Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients

La maladie cœliaque : une maladie auto-immune induite par un antigène alimentaire

CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes

Contact Info

Product

Resources

About