TY - JOUR
T1 - Multicolor flow-cytometric analysis of milk allergen-specific T-helper type 2 cells revealed coexpression of interleukin-4 with Foxp3
AU - Yamawaki, Kazuo
AU - Inuo, Chisato
AU - Nomura, Takayasu
AU - Tanaka, Kenichi
AU - Nakajima, Yoichi
AU - Kondo, Yasuto
AU - Yoshikawa, Tetsushi
AU - Urisu, Atsuo
AU - Tsuge, Ikuya
N1 - Publisher Copyright:
© 2015 American College of Allergy, Asthma & Immunology.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background Allergen-specific T-helper type 2 (TH2) cells play an important role in the development of allergic inflammation; however, investigations of the properties of allergen-specific T cells have been challenging in humans. Despite clear evidence that forkhead box p3 (Foxp3) is expressed in conventional effector T cells, its function has remained unknown. Objective To characterize allergen-specific TH2 cells in milk allergy, with particular focus on the expression of Foxp3. Methods Twenty-one children with milk allergy and 11 children without milk allergy were studied. Peripheral blood mononuclear cells from subjects were stimulated with milk allergen for 6 hours and analyzed using multicolor flow cytometry to identify CD154+ allergen-specific T-helper cells. Simultaneously, the expression of intracellular cytokines and Foxp3 was analyzed. Results The milk allergy group had significantly larger numbers of milk allergen-specific interleukin (IL)-4- and IL-5-producing CD4+ T cells than the control group. Subjects in the milk allergy group had significantly more CD154+CD4+ IL-10-producing cells and CD154+Foxp3+CD4+ cells than those in the control group. In addition, the number of milk allergen-specific CD154+Foxp3+CD4+ cells strongly correlated with that of CD154+IL4+CD4+ cells. Bcl-2 expression in CD154+IL-4+Foxp3+ T-helper cells was significantly lower compared with that in total CD4 cells. Conclusion Increased numbers of IL-4-producing allergen-specific T-helper cells were found in patients with milk allergy. In addition, Foxp3 was coexpressed with IL-4 in allergen-specific TH2 cells from patients. This coexpression was associated with lower Bcl-2 levels and could contribute to the phenotype and function of TH2 cells.
AB - Background Allergen-specific T-helper type 2 (TH2) cells play an important role in the development of allergic inflammation; however, investigations of the properties of allergen-specific T cells have been challenging in humans. Despite clear evidence that forkhead box p3 (Foxp3) is expressed in conventional effector T cells, its function has remained unknown. Objective To characterize allergen-specific TH2 cells in milk allergy, with particular focus on the expression of Foxp3. Methods Twenty-one children with milk allergy and 11 children without milk allergy were studied. Peripheral blood mononuclear cells from subjects were stimulated with milk allergen for 6 hours and analyzed using multicolor flow cytometry to identify CD154+ allergen-specific T-helper cells. Simultaneously, the expression of intracellular cytokines and Foxp3 was analyzed. Results The milk allergy group had significantly larger numbers of milk allergen-specific interleukin (IL)-4- and IL-5-producing CD4+ T cells than the control group. Subjects in the milk allergy group had significantly more CD154+CD4+ IL-10-producing cells and CD154+Foxp3+CD4+ cells than those in the control group. In addition, the number of milk allergen-specific CD154+Foxp3+CD4+ cells strongly correlated with that of CD154+IL4+CD4+ cells. Bcl-2 expression in CD154+IL-4+Foxp3+ T-helper cells was significantly lower compared with that in total CD4 cells. Conclusion Increased numbers of IL-4-producing allergen-specific T-helper cells were found in patients with milk allergy. In addition, Foxp3 was coexpressed with IL-4 in allergen-specific TH2 cells from patients. This coexpression was associated with lower Bcl-2 levels and could contribute to the phenotype and function of TH2 cells.
UR - http://www.scopus.com/inward/record.url?scp=84949746503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949746503&partnerID=8YFLogxK
U2 - 10.1016/j.anai.2015.09.020
DO - 10.1016/j.anai.2015.09.020
M3 - Article
C2 - 26507707
AN - SCOPUS:84949746503
SN - 1081-1206
VL - 115
SP - 503
EP - 508
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 6
ER -