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

Zhu X, Wang M, Crump CH, Mishra A. An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice. Am J Physiol Gastrointest Liver Physiol 297: G550-G558, 2009. First published July 1, 2009; doi: 10.1152/ajpgi.00148.2009.-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(+) CD45RB(high) effector T cells in allergen-challenged mice increased compared with saline-challenged mice (65.4 +/- 3.6 x 10(3) to 44.8 +/- 4.2 x 10(3)), whereas CD4(+) CD45RB(low) mostly regulatory T cells decreased in allergen-challenged mice compared with saline-challenged mice (5.8 +/- 0.9 x 10(3) from 10.2 +/- 1.7 x 10(3)). 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(+) CD45RB(low) cells in allergen-challenged mice compared with saline-challenged mice was observed. The reduced IL-2 in the CD4(+) CD45RB(low) subset may be associated with reduction of CD4(+) CD45RB(low) subset. In conclusion, our results suggest that local regulatory interaction of CD45RB(high) and CD45RB(low) CD4(+) T cells may be required for protective and pathogenic immunity in EE.