Defective suppression of Th2 cytokines by CD4+CD25+ regulatory T cells in birch allergics during birch pollen season
Defective suppression of Th2 cytokines by CD4+CD25+ regulatory T cells in birch allergics during birch pollen season
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DOI：
10.1111/j.1365-2222.2004.02067.x
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发表时间：
2004-09-01
影响因子：
6.1
通讯作者：
Rudin, A
中科院分区：
文献类型：
--
作者：
Grindebacke, H;Wing, K;Rudin, A
背景CD4(+)CD25(+)调节性T细胞抑制人T细胞对自身抗原和外源抗原的增殖和细胞因子产生。人类新生儿缺乏这些细胞会导致多种自身免疫性疾病和炎症性疾病以及 IgE 水平升高。然而，它们在人类过敏性疾病中的作用仍不清楚。 目的 本研究旨在评估相对于非过敏对照，CD4(+)CD25(+)调节性T细胞在桦树花粉季节外和桦树花粉季节期间抑制增殖和细胞因子产生的能力。方法从13名桦树过敏患者和6名非过敏对照的血液中获取CD4(+)细胞在花粉季节外和10桦树花粉季节期间的桦树过敏患者和 10 名非过敏对照。用磁珠纯化CD25(+)和CD25(-)级分，将细胞级分单独或以不同比例一起与抗原呈递细胞和桦树花粉提取物或抗CD3抗体一起培养。分别通过胸苷掺入和ELISA测量IFN-γ、IL-13、IL-5和IL-10的增殖和水平。通过流式细胞术分析CD25(+)细胞的数量。结果来自过敏者和非过敏者的CD4(+)CD25(+)调节性T细胞在桦树花粉季节之外和期间均有效抑制了对桦树过敏原的T细胞增殖。然而，在季节期间，来自过敏患者而非非过敏对照的CD4(+)CD25(+)调节性T细胞在下调桦树花粉诱导的IL-13和IL-5产生方面存在缺陷，同时保留了抑制IFN-γ产生的能力。相比之下，在花粉季节之外，过敏者和非过敏对照的调节细胞都能够抑制辅助性T细胞2细胞因子的产生。结论这是第一项显示Th1和Th2细胞因子差异抑制的研究，来自桦树花粉过敏患者的CD4(+)CD25(+)调节性T细胞在桦树花粉季节期间无法下调Th2反应，但不能下调Th1反应。
Background CD4(+)CD25(+) regulatory T cells suppress proliferation and cytokine production by human T cells both to self-antigens and exogenous antigens. Absence of these cells in human newborns leads to multiple autoimmune and inflammatory disorders together with elevated IgE levels. However, their role in human allergic disease is still unclear.Objective This study aimed to evaluate the capacity of CD4(+)CD25(+) regulatory T cells to suppress proliferation and cytokine production outside and during birch-pollen season in birch-allergic patients relative to non-allergic controls.Methods CD4(+) cells were obtained from blood of 13 birch-allergic patients and six non-allergic controls outside pollen season and from 10 birch-allergic patients and 10 non-allergic controls during birch-pollen season. CD25(+) and CD25(-) fractions were purified with magnetic beads and cell fractions, alone or together in various ratios, were cultured with antigen-presenting cells and birch-pollen extract or anti-CD3 antibody. Proliferation and levels of IFN-gamma, IL-13, IL-5 and IL-10 were measured by thymidin incorporation and ELISA, respectively. Numbers of CD25(+) cells were analysed by flow cytometry.Results CD4(+)CD25(+) regulatory T cells from both allergics and non-allergics potently suppressed T cell proliferation to birch allergen both outside and during birch-pollen season. However, during season CD4(+)CD25(+) regulatory T cells from allergic patients but not from non-allergic controls were defective in down-regulating birch pollen induced IL-13 and IL-5 production, while their capacity to suppress IFN-gamma production was retained. In contrast, outside pollen season the regulatory cells of both allergics and non-allergic controls were able to inhibit T-helper 2 cytokine production.Conclusion This is the first study to show differential suppression of Th1 and Th2 cytokines, with CD4(+)CD25(+) regulatory T cells from birch-pollen-allergic patients being unable to down-regulate Th2, but not Th1 responses during birch-pollen season.