Submitted on April 21, 2009
Revised on June 25, 2009
Accepted on June 25, 2009
An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice
Xiang Zhu1, Meiqin Wang1, Caleb H Crump1, and Anil Mishra1*
1 Cincinnati Childrens Hospital Medical Center
* To whom correspondence should be addressed. E-mail: anil.mishra{at}cchmc.org.
We recently reported a critical role for T cells in the induction of eosinophilic esophagitis (EE); 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. FACS analysis was performed to examine activated T cell subsets using the cell surface activation markers CD25, 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+CD45rbhighFOXP3- effector T cells in allergen challenged mice increased compared to saline challenged mice (8.4 ± 2.0 X 103 to 32.6 ± 2.3 X 103); whereas, CD4+CD45RBlowFOXP3+ regulatory T cells decreased in allergen challenged mice compared to saline challenged mice (1.6 ± 0.5 X 102 from 6.2 ± 0.4 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. Additionally, a significantly reduced IL-2 production by CD4+CD45RBlow cells in allergen challenged mice compared to saline challenged mice was noticed. 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 required for protective and pathogenic immunity in EE.
