ArticleThe American journal of gastroenterology2011
CD62L(neg)CD38⁺ expression on circulating CD4⁺ T cells identifies mucosally differentiated cells in protein fed mice and in human celiac disease patients and controls.
Article in The American journal of gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Dietary gluten triggers concomitant activation of CD4+ and CD8+ αβ T cells and γδ T cells in celiac disease.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Plasma lipopolysaccharide-binding protein (LBP), a proxy for intestinal permeability, relates to clinicopathological and immunological disease activity in inflammatory bowel disease patients at diagnosis and during disease course.Journal of Crohn's & colitis · 2026Article
- A laboratory test to detect gliadin-specific CD4Journal of translational autoimmunity · 2025Article
- CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor.Science advances · 2025Article
- The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2-associated multisystem inflammatory syndrome in children.The Journal of clinical investigation · 2023Article
- CPHEN-016: Comprehensive phenotyping of human regulatory T cells.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2022Article
- Analytical and functional approaches to assess the immunogenicity of gluten proteins.Frontiers in nutrition · 2022Review
- Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T-Cell-Directed Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Celiac Disease Defined by Over-Sensitivity to Gliadin Activation and Superior Antigen Presentation of Dendritic Cells.International journal of molecular sciences · 2021Article
- Review
- CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity.Frontiers in immunology · 2020Review
- CD38 expression on gluten-specific T cells is a robust marker of gluten re-exposure in coeliac disease.United European gastroenterology journal · 2019Article
- Can molecular stratification improve the treatment of inflammatory bowel disease?Pharmacological research · 2019Review
- Distinct phenotype of CD4Nature medicine · 2019Article
- Frequencies of circulating regulatory TIGITMucosal immunology · 2019Article
- HIV Disease Progression: Overexpression of the Ectoenzyme CD38 as a Contributory Factor?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Systemic innate immune activation in food protein-induced enterocolitis syndrome.The Journal of allergy and clinical immunology · 2017Article
- TCR sequencing of single cells reactive to DQ2.5-glia-α2 and DQ2.5-glia-ω2 reveals clonal expansion and epitope-specific V-gene usage.Mucosal immunology · 2016Article
- Cutting edge: progesterone directly upregulates vitamin d receptor gene expression for efficient regulation of T cells by calcitriol.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- CD38 is expressed on inflammatory cells of the intestine and promotes intestinal inflammation.PloS one · 2015Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
objectivesThe aim of this study was to identify new markers of mucosal T cells to monitor ongoing intestinal immune responses in peripheral blood.
methodsExpression of cell-surface markers was studied in mice on ovalbumin (OVA)-specific T cells in the gut-draining mesenteric lymph nodes (MLN) after OVA feed. The effect of the local mucosal mediators retinoic acid (RA) and transforming growth factor-β (TGF-β) on the induction of a mucosal phenotype was determined in in vitro T-cell differentiation assays with murine and human T cells. Tetramer stainings were performed to study gluten-specific T cells in the circulation of patients with celiac disease, a chronic small-intestinal inflammation.
resultsIn mice, proliferating T cells in MLN were CD62L(neg)CD38(+) during both tolerance induction and abrogation of intestinal homeostasis. This mucosal CD62L(neg)CD38(+) T-cell phenotype was efficiently induced by RA and TGF-β in mice, whereas for human CD4(+) T cells RA alone was sufficient. The CD4(+)CD62L(neg)CD38(+) T-cell phenotype could be used to identify T cells with mucosal origin in human peripheral blood, as expression of the gut-homing chemokine receptor CCR9 and β(7) integrin were highly enriched in this subset whereas expression of cutaneous leukocyte-associated antigen was almost absent. Tetramer staining revealed that gluten-specific T cells appearing in blood of treated celiac disease patients after oral gluten challenge were predominantly CD4(+)CD62L(neg)CD38(+). The total percentage of circulating CD62L(neg)CD38(+) of CD4 T cells was not an indicator of intestinal inflammation as percentages did not differ between pediatric celiac disease patients, inflammatory bowel disease patients and respective controls. However, the phenotypic selection of mucosal T cells allowed cytokine profiling as upon restimulation of CD62L(neg)CD38(+) cells interleukin-10 (IL-10) and interferon-γ (IFN-γ) transcripts were readily detected in circulating mucosal T cells.
conclusionsBy selecting for CD62L(neg)CD38(+) expression that comprises 5-10% of the cells within the total CD4(+) T-cell pool we are able to highly enrich for effector T cells with specificity for mucosal antigens. This is of pivotal importance for functional studies as this purification enhances the sensitivity of cytokine detection and cellular activation.
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