Journal of Pediatric Gastroenterology & Nutrition:
*Division of Allergy and Immunology, University of Cincinnati
†Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Address correspondence and reprint requests to Marc E. Rothenberg, MD, PhD, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, ML7028, Cincinnati, OH 45229 (e-mail: Rothenberg@cchmc.org).
Received 22 October, 2012
Accepted 23 October, 2012
The authors report no conflicts of interest.
See “Markers of Antigen Presentation and Activation on Eosinophils and T Cells in the Esophageal Tissue of Patients With Eosinophilic Esophagitis” by Le-Carlson et al on page 257.
In the present issue of JPGN, Le-Carlson et al (1) demonstrate the presence of costimulatory markers on eosinophils (CD40 and CD80) and activation markers on T cells (CD28 and CD69) in the esophageal epithelia of patients with eosinophilic esophagitis (EoE). These data are in line with previous work that has shown the presence and importance of T cells in EoE and that eosinophils express major histocompatibility complex type II molecules (2–5). Collectively, the present and previous data imply, but do not prove, that eosinophils have a role in antigen presentation to T cells as part of the pathophysiology in EoE. The idea of eosinophils as antigen-presenting cells, rather than their common classification as innate effector cells, is not new (6,7) and suggests a network in which eosinophils have multiple roles including modulating, stimulating, and effector functions for both innate and adaptive immunity. Although the authors show higher numbers of cells with activation and costimulatory markers in EoE versus gastroesophageal reflux disease (GERD) and healthy controls, it is notable that the percentage of these cells did not increase. This finding suggests that this activation is not unique to EoE but is a phenomenon of the esophagus, which has implications for other esophageal disorders, such as GERD. Unfortunately, the present study only uses 1 approach, tissue-based immunostaining, which can often be problematic because of nonspecific staining. Additionally, the present study does little to address the involved mechanisms.
Accordingly, this preliminary work leaves many unanswered questions. One such question is which occurs first, eosinophil or T-cell infiltration into the esophagus? Because dendritic cells can instruct T cells, which in turn can instruct B cells, both via the T-cell receptor–major histocompatibility complex type II interaction, it is interesting to consider the order of events. In this context, how may antigen presentation by eosinophils differ from antigen presentation by other cells? Also, how may activated T cells augment eosinophil activity? Furthermore, what type of T cells would form this immune synapse with eosinophils? In other words, are these T cells regulatory, effector, naïve, or memory?
The answers to these questions have potential clinical implications. Understanding the role of particular cells in the pathophysiology of EoE will hopefully lead to more targeted therapies. For instance, recognizing eosinophils as antigen-presenting cells that induce T-cell activation suggests that targeting this process may be therapeutic. Indeed, previous studies have shown that immunosuppressants may have effects on T cells in EoE (8). Likewise, a therapy such as swallowed tacrolimus may target esophageal T cells. In addition, targeting the immune synapse may also be a possible therapy. Although there are present biologic therapies that do target some of the markers studied in this article, such as anti-CD40 and anti-CD40L (9), these therapies have broad effects on the immune system and can carry serious adverse effects. Therefore, it may be beneficial to consider approaches for local delivery in the esophagus. Thus, a more detailed understanding of this potentially unique immune synapse between eosinophils and T cells may ultimately lead to additional therapeutic targets.
1. Le-Carlson M, Seki S, Abarbanel D, et al. Markers of antigen presentation and activation on eosinophils and T-cells in the esophageal tissue of patients with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr
2. Mishra A, Schlotman J, Wang M, et al. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol
3. Tantibhaedhyangkul U, Tatevian N, Gilger MA, et al. Increased esophageal regulatory T cells and eosinophil characteristics in children with eosinophilic esophagitis and gastroesophageal reflux disease. Ann Clin Lab Sci
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5. Patel AJ, Fuentebella J, Gernez Y, et al. Increased HLA-DR expression on tissue eosinophils in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr
6. Wang H-B, Ghiran I, Matthaei K, et al. Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol
7. Hansel TT, Braunstein JB, Walker C, et al. Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR. Clin Exp Immunol
8. Netzer P, Gschossmann JM, Straumann A, et al. Corticosteroid-dependent eosinophilic oesophagitis: azathioprine and 6-mercaptopurine can induce and maintain long-term remission. Eur J Gastroenterol Hepatol
9. Law C-L, Grewal IS. Therapeutic interventions targeting CD40L (CD154) and CD40: the opportunities and challenges. Adv Exp Med Biol