An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice.
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.
Zhu
Xiang
X
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Wang
Meiqin
M
Crump
Caleb H
CH
Mishra
Anil
A
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001232:Aspergillus fumigatus; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology* / Q000382:microbiology; D004941:Esophagitis / Q000276:immunology* / Q000382:microbiology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000382:microbiology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016753:Interleukin-10; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015847:Interleukin-4; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D012333:RNA, Messenger; D000099192:CD69 Antigens