Markers of Antigen Presentation and Activation on Eosinophils and T-Cells in the Esophageal Tissue of Patients with Eosinophilic Esophagitis.
ABSTRACT OBJECTIVES:: Evidence suggests eosinophils may be acting as antigen presenting cells (APC) by presenting antigen to T-cells. We investigated the surface proteins of eosinophils and T-cells in the esophageal biopsies of eosinophilic eosphagitis (EoE) patients, gastroeosphageal reflux (GERD) patients, and healthy controls. METHODS:: Subjects were categorized as EoE, GERD or healthy control (HC). In esophageal tissue, EG2+ eosinophils were stained for the antigen presenting cell markers, CD40 or CD80, via immunohistochemistry. CD3+ T-cells were stained for co-stimulatory markers CD40L or CD28, and for activation markers, CD69 or CD134 via immunofluorescence or immunohistochemistry. RESULTS:: Eosinophils stained with CD40 and CD80. The number of EG2+CD40+ cells was increased in EoE (mean = 19.1 ± 14.8 cells/HPF, n = 11), in comparison to GERD (mean = 0.13 ± 0.19 cells/HPF, n = 5, p < 0.01) and HC (mean = 0.3 ± 0.7 cells/HPF, n = 5, p < 0.01). There was an elevation in EG2+CD80+ cells in EoE (mean = 18.1 ± 16.2 cells/HPF, n = 10), GERD (mean = 1.7 ± 2.8 cells/HPF, n = 6, p < 0.01) or HC (mean = 0.8 ± 1.3 cells/HPF, n = 6, p < 0.01). CD3+ T-cells stained with CD40L (not quantified). CD3+ T-cells stained with CD28 at elevated levels in EoE (mean = 14 ± 8.7 cells/HPF, n = 9), versus GERD (mean = 3.3 ± 1.2 cells/HPF, n = 6, p < 0.05) or HC (mean = 3.0 ± 3.2 cells/HPF, n = 7, p < 0.01). The number of CD3+CD69+ cells was highest in EoE (mean = 14.8 ± 7.5 cells/HPF, n = 6) versus GERD (mean = 0.8 ± 0.9 cells/HPF, n = 6, p < 0.001) or HC (mean = 2.7 ± 2.5 cells/HPF, n = 6, p < 0.001). CONCLUSIONS:: We show that esophageal eosinophils express CD40 and CD80, and T-cells with CD40L, CD28 and CD69. The number of double stained cells was higher in EoE in comparison to controls groups. These data support the hypothesis that eosinophils in EoE might act as APC, activating T-cells.
- Journal of pediatric gastroenterology and nutrition 11/2012; DOI:10.1097/MPG.0b013e31827ab8d3 · 2.87 Impact Factor
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ABSTRACT: Eosinophilic esophagitis (EoE) has become a common gastrointestinal disease. It is characterized by severe eosinophil infiltration in the esophagus. EoE is strongly associated with food allergy, asthma, atopic dermatitis, and other allergic diseases. T lymphocytes, especially Th2 cells, play an instrumental role in the development of allergic inflammation. Recent studies have shown that the ligation of co-stimulatory molecules contributes to the activation, differentiation, and proliferation of T cells. In this review, we will discuss the growing evidence of co-stimulatory molecules including OX40, Light, and HVEM in the pathogenesis of Th2-driven EoE. Our goal is to provide the rationale for the development of novel therapy therapies that target co-stimulatory molecules.Digestive Diseases and Sciences 03/2013; 58(6). DOI:10.1007/s10620-013-2599-8 · 2.55 Impact Factor
- Digestive Diseases and Sciences 04/2013; 58(6). DOI:10.1007/s10620-013-2679-9 · 2.55 Impact Factor