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

Abstract

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 × 103 to 44.8 ± 4.2 × 103), whereas CD4+CD45RBlow mostly regulatory T cells decreased in allergen-challenged mice compared with saline-challenged mice (5.8 ± 0.9 × 103 from 10.2 ± 1.7 × 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.