Frequency of Foxp3+CD4CD25+ T cells is associated with the phenotypes of allergic asthma.
OBJECTIVE
A forkhead/winged-helix family transcriptional repressor, Foxp3, is highly expressed on CD4(+)CD25(+) T regulatory cells. The role of Foxp3(+)CD4(+)CD25(+) T regulatory cells in asthma remains to be elucidated. Using mouse models and peripheral blood mononuclear cells (PBMC) from subjects with allergic asthma, we aimed to explore whether Foxp3(+)CD4(+)CD25(+) T regulatory cells associate with asthma phenotypes.


METHODS
Foxp3(+)CD4(+)CD25(+) T cells were detected by FACS and the correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and asthma phenotypes was assessed.


RESULTS
The frequency of Foxp3(+)CD4(+)CD25(+) T cells among total CD4(+)CD25(+) T cells in the lungs showed an inverse correlation with eosinophilic inflammation in BALB/c, A/J and C57BL/6 strains. In addition, the frequency of Foxp3(+)CD4(+)CD25(+) T cells was inversely correlated with BHR and allergen-specific IgE levels in the serum of A/J mice. In BALB/c mice, the frequency of Foxp3(+)CD4(+)CD25(+) T cells correlated with the level of IL-10 in BAL fluid. The inverse correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and eosinophilic inflammation disappeared when mice were treated with anti-IL-10 receptor mAb during allergen challenge. Interestingly, intracellular cytokine staining of lung cells revealed that IL-10 was predominantly produced by Foxp3(-)CD4(+)CD25(+) T cells. The frequency of Foxp3(+)CD4(+)CD25(+) T cells among total CD4(+)CD25(+) T cells in PBMC of asthmatics was significantly lower than that of healthy subjects, although there was no significant correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and asthma severity.


CONCLUSIONS
These results suggest a role for lung Foxp3(+)CD4(+)CD25(+) T cells in the regulation of asthma phenotypes, presumably through an IL-10-mediated mechanism.
Matsumoto
Koichiro
K
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Inoue
Hiromasa
H
Fukuyama
Satoru
S
Kan-O
Keiko
K
Eguchi-Tsuda
Miyuki
M
Matsumoto
Takafumi
T
Moriwaki
Atsushi
A
Nakano
Takako
T
Nakanishi
Yoichi
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D015704:CD4 Antigens / Q000378:metabolism*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010641:Phenotype; D012130:Respiratory Hypersensitivity / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10