Xu Geng, Mou Zhonglin, Jiang Hongyan, Cheng Lei, Shi Jianbo, Xu Rui, Oh Yun, Li Huabin
Otorhinolaryngology Hospital of The First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Laryngoscope. 2007 May;117(5):876-80. doi: 10.1097/MLG.0b013e318033f99a.
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.
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.
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).
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.
变应性鼻炎(AR)是以Th2为主导的疾病,其发病机制仍知之甚少。CD4(+)CD25(+) T细胞约占外周血CD4(+) T细胞的5%至10%,已被证明可调节外周效应T细胞的激活。CD4(+)CD25(+) T细胞的活性与转录因子Foxp3相关。本研究旨在评估CD4(+)CD25(+) T细胞以及Foxp3在AR发病机制中的可能作用。
从17例AR患者和11例对照受试者中获取鼻组织和外周血单个核细胞(PBMC)。通过免疫组织化学和实时逆转录聚合酶链反应(RT-PCR)检测鼻组织中的Foxp3。使用流式细胞术评估PBMC中的CD4(+)CD25(+) T细胞和Foxp3。在有或无佛波酯(PMA)和离子霉素刺激的情况下,通过酶联免疫吸附测定(ELISA)测量培养的PBMC中白细胞介素-2(IL-2)和干扰素-γ(IFN-γ)的浓度。
两组鼻黏膜中Foxp3(+)细胞数量分别为129.5±35.6和44.2±±20.5个/mm(2)(P <.05)。与对照组相比,AR患者中Foxp3(+)淋巴细胞较少且Foxp3 mRNA降低(P <.05)。两组PBMC中CD4(+)CD25(+)群体的频率分别为1.99±0.95%和3.55±1.27%(P <.05)。两组PBMC中Foxp3(+)CD4(+) CD25(+)群体的频率(1.81±0.77对3.37±1.04,P <.05)和Foxp3的平均荧光强度(MFI)(5.93±2.64对11.72±4.29,P <.05)存在显著差异。刺激后,AR患者PBMC中IL-和IFN-γ的浓度分别为182.72±85.11 pg/mL和348.94±151.88 pg/mL,而对照组分别为90.6±61.5 pg/mL和155.64±68.33 pg/mL(P <.05)。
我们的结果表明,CD4(+) CD25(+)调节性T细胞以及Foxp3可能在AR的免疫失衡中起关键作用。这些发现表明,增加Foxp3和CD4(+)CD25(+) T细胞有可能成为治疗AR的新治疗靶点。