Markers of antigen presentation and activation on eosinophils and T cells in the esophageal tissue of patients with eosinophilic esophagitis.
OBJECTIVE
Evidence suggests eosinophils may be acting as antigen-presenting cells (APCs) by presenting antigen to T cells. We investigated the surface proteins of eosinophils and T cells in the esophageal biopsies of patients with eosinophilic esophagitis (EoE), patients with gastroesophageal reflux disease (GERD), and healthy controls (HCs).


METHODS
: Subjects were categorized as EoE, GERD, or HC. In esophageal tissue, EG2+ eosinophils were stained for the APC markers, CD40 or CD80, via immunohistochemistry. CD3+ T cells were stained for costimulatory 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/high-power field [HPF], n=11), compared with 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 control groups. These data support the hypothesis that eosinophils in EoE may act as APCs, activating T cells.
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Stanford University Medical Center, Lucile Packard Children's Hospital, Palo Alto, CA, USA. lecarlsonm@gmail.com
Minou
M
Le-Carlson
Scott
S
Seki
David
D
Abarbanel
Antonio
A
Quiros
Kenneth
K
Cox
Kari C
KC
Nadeau
D000293:Adolescent; D000328:Adult; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D057765:Eosinophilic Esophagitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D015415:Biomarkers