Insufficient increment of CD4+CD25+ regulatory T cells after stimulation in vitro with allergen in allergic asthma.
BACKGROUND
Allergen exposure can lead to the development of allergic asthma, sensitized asymptomatic or nonallergic responses in different conditions. Regulatory T (T(reg)) cells are involved in controlling the immune response direction. The aim of this study was to determine whether allergic asthmatics had defects in CD4+CD25+ T(reg) cells and CD4+IL (interleukin)-10+ T(reg) cells after specific allergen exposure.


METHODS
Peripheral-blood mononuclear cells (PBMCs) were isolated from 20 patients with asthma sensitized to house dust mite, 24 asymptomatic subjects sensitized to house dust mite and 22 nonallergic subjects. Cells were cultured without stimulation and with rDer p 1. Frequencies and proliferations of CD4+CD25+ T cells and CD4+IL-10+ T cells were measured by flow cytometry. Concentrations of IL-10, IL-4, interferon (IFN)-gamma and tumor growth factor beta(1) in culture supernatants and sera were determined by ELISA.


RESULTS
PBMCs derived from sensitized asthmatic patients had the lowest percentage of CD4+CD25+ T(reg) cells and the highest IL-4 level in response to allergen among the 3 groups. PBMCs derived from sensitized asymptomatic subjects had higher percentages of both CD4+CD25+ T(reg) cells and CD4+IL-10+ T cells than those from sensitized asthmatic patients in rDer-p-1-stimulated cultures, and they had the highest levels of IL-10 and IFN-gamma responses to allergen among the 3 groups.


CONCLUSIONS
Patients with allergic asthma had an insufficient CD4+CD25+ T(reg) cell response and an excessive Th2 response to specific allergen. The high levels of T(reg) cell response and IL-10 and IFN- gamma responses to specific allergen can partly explain the immunological characteristics associated with sensitized asymptomatic subjects.
Section of Respiratory Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
Li-Hui
LH
Wang
Yu-Hui
YH
Lin
Jiong
J
Yang
Wei
W
Guo
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology; D060829:Arthropod Proteins; D001249:Asthma / Q000097:blood / Q000276:immunology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D015847:Interleukin-4 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism; D055815:Young Adult
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508598:IL4 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D010835:Phytohemagglutinins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1