Markers of antigen presentation and activation on eosinophils and T cells in the esophageal tissue of patients with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an emerging clinicopathologic disease characterized by the abnormal infiltration of eosinophils into the esophageal mucosa. EoE typically presents with nonspecific upper gastrointestinal symptoms such as emesis, poor feeding, and epigastric pain, and can clinically be indistinguishable from gastroesophageal reflux disease (GERD). As supported by the high association with other atopic conditions such as asthma and food allergies, EoE is believed to be triggered by food and environmental allergens, implying an interaction between adaptive immunity, that is the T cells, and eosinophils. The underlying pathogenesis of EoE is not well characterized; specifically, how eosinophils interact with T cells remains unknown (1,2). Previous work from our laboratory and other supports T-cell involvement in the disease pathogenesis of EoE (3). Increased levels of CD3+FoxP3+ cells were found in the esophageal biopsies of patients with EoE, compared with healthy controls (HCs) and patients with GERD. Additionally, performing real-time quantitative polymerase chain reaction assays on the RNA purified from esophageal biopsies revealed 1.5-fold higher FoxP3 mRNA expression in EoE in comparison with control groups (4). Additional studies on esophageal biopsies investigate the role of eosinophils in local inflammation. Recent data suggest that eosinophils in several allergic conditions may be acting as antigen-presenting cells (APCs) by presenting processed antigen to T cells and initiating the inflammatory cascade (Fig. 1) (5–10). Previous work from our laboratory found major histocompatibility complex (MHC) class II molecules or human leukocyte antigen, HLA-DR, expressed on eosinophils. Moreover, the proportion of HLA-DR expression was found to be higher in EoE than in either HC or GERD groups, suggesting eosinophils may be playing a role in antigen presentation (11). Figure 1 Schematic of T-cell and antigen-presenting cell (APC) interaction. TCR = T-cell receptor, CD28 and CD40L, and MHC II = major histocompatiblity complex, CD80 and CD40 on T cells and APC, respectively. In the present study, we hypothesized that eosinophils may act at APCs and activate T cells. To test this, we studied whether costimulatory markers CD28 and CD40L (typical of T cells), and CD80 and CD40 (typical of APCs), were present on eosinophils and T cells, respectively, from subjects with EoE. In the same samples, we also investigated several markers of T-cell activation including CD 69, the earliest inducible marker of activation, and CD134, an acute marker that occurs within days. Studies were performed on esophageal biopsies of subjects with EoE and compared with those of patients with GERD and HCs.