A possible role of CD4+CD25+ T cells as well as transcription factor Foxp3 in the dysregulation of allergic rhinitis.
BACKGROUND
Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4(+)CD25(+) T cells account for approximately 5% to 10% peripheral CD4(+) T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4(+)CD25(+) T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4(+)CD25(+) T cells as well as Foxp3 in the pathogenesis of AR.


METHODS
Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4(+)CD25(+) T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin.


RESULTS
The numbers of Foxp3(+) cells was 129.5 +/- 35.6 and 44.2 +/- 20.5 cells/mm(2) in nasal mucosa of two groups (P < .05). There were less Foxp3(+) lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4(+)CD25(+) population in PBMCs of two groups were 1.99 +/- 0.95% and 3.55 +/- 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3(+)CD4(+) CD25(+) population (1.81 +/- 0.77 vs 3.37 +/- 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 +/- 2.64 vs 11.72 +/- 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-gamma were 182.72 +/- 85.11 pg/mL and 348.94 +/- 151.88 pg/mL in PBMCs with AR, while those were 90.6 +/- 61.5 pg/mL and 155.64 +/- 68.33 pg/mL in controls (P < .05).


CONCLUSIONS
Our results indicate that CD4(+) CD25(+) regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4(+)CD25(+) T cells have the potential to be new therapeutic targets for the treatment of AR.
Xu
Geng
G
Otorhinolaryngology Hospital of The First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Mou
Zhonglin
Z
Jiang
Hongyan
H
Cheng
Lei
L
Shi
Jianbo
J
Xu
Rui
R
Oh
Yun
Y
Li
Huabin
H
D000328:Adult; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma