CD4 +CD45RB Low T Cells Are Critical In Regulating Esophageal Eosinophilia In Mice

Abstract

RATIONALE: Eosinophilic esophagitis (EE) is an emerging disease and we previously demonstrated that adaptive T cell immunity is critical in the disease pathogenesis. However, the specific subsets of T cells that promote esophageal eosinophilia are not yet understood. Therefore, we focused our studies to examine the role of CD45RB T subsets, as the pathogenic and regulatory activity of T cells depends on the expression levels of CD45RB. METHODS: A flow cytometric analysis was performed to examine the frequency of CD45RBhigh and CD45RBlow T cell subsets in the mouse esophagus. A real time PCR analysis was performed to examine the pathogenic and anti-inflammatory characteristics of both subsets of T cells. In addition, we adoptively transferred these purified cell subsets in mice with experimental EE and examined their role in the disease pathogenesis. RESULTS: An increase of CD4+CD45RBhigh and a decrease of CD4+CD45RBlow cells were observed in mouse esophagus following the induction of experimental EE. A relatively high transcript level of IL-5 and IL-13 in CD4+CD45RBhigh and IL-10 and TGF-β1 in CD4+CD45RBlow spleen purified cells was observed. Further, our initial experimentation revealed that mice adoptively transferred with 4X105 CD4+CD45RBlow T cells/week were protected from the induction of esophageal eosinophilia compared to control mice that did not received adoptively transferred cells. Mice receiving CD4+CD45RBhigh T cell had no significant change in the number of eosinophils in the esophagus compared to control mice following allergen challenge. CONCLUSIONS: CD4+CD45RBlow T cells have a critical role in down-regulating allergen-induced eosinophil recruitment to the mouse esophagus.