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Am J Physiol Gastrointest Liver Physiol 297: G550-G558, 2009. First published July 1, 2009; doi:10.1152/ajpgi.00148.2009
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INFLAMMATION/IMMUNITY/MEDIATORS

An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice

Xiang Zhu,* Meiqin Wang,* Caleb H. Crump, and Anil Mishra

Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio

Submitted 21 April 2009 ; accepted in final form 25 June 2009

We recently reported a critical role for T cells in the induction of eosinophilic esophagitis (EE) in mice; however, the role of specific T cell subsets in disease pathogenesis is not yet understood. In the current study, we tested the hypothesis that allergen-induced EE develops in response to the disproportion of functionally different effector and regulatory T cells in the esophagus. Fluorescence-activated cell sorter analysis was performed to examine activated T cell subsets using the cell surface activation markers CD25 and CD69. A significant increase in activated CD4+ and CD4 T cells was observed in the total esophageal cells isolated from the mouse model of EE. Furthermore, an imbalance in the effector and regulatory T cells was observed in the esophagus. The esophageal CD4+CD45RBhigh effector T cells in allergen-challenged mice increased compared with saline-challenged mice (65.4 ± 3.6 x 103 to 44.8 ± 4.2 x 103), whereas CD4+CD45RBlow mostly regulatory T cells decreased in allergen-challenged mice compared with saline-challenged mice (5.8 ± 0.9 x 103 from 10.2 ± 1.7 x 103). The functional characteristics were examined by analysis of the pro- and anti-inflammatory cytokine profile of purified low and high CD4+CD45RB subsets from the spleen. Additionally, a significantly reduced interleukin (IL)-2 production by CD4+CD45RBlow cells in allergen-challenged mice compared with saline-challenged mice was observed. The reduced IL-2 in the CD4+CD45RBlow subset may be associated with reduction of CD4+CD45RBlow subset. In conclusion, our results suggest that local regulatory interaction of CD45RBhigh and CD45RBlow CD4+ T cells may be required for protective and pathogenic immunity in EE.

allergen; effector T cell; eosinophils; esophagitis; regulatory T cell



Address for reprint requests and other correspondence: A. Mishra, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., MLC 7028, Cincinnati, OH 45229 (e-mail: Anil.Mishra{at}cchmc.org)







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