Allergen-driven limiting dilution analysis of human IL-4 and IFN-gamma production in allergic rhinitis and clinically tolerant individuals.

Allergen-driven limiting dilution analysis of human IL-4 and IFN-gamma production in allergic rhinitis and clinically tolerant individuals.
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对过敏性鼻炎和临床耐受个体中人 IL-4 和 IFN-γ 产生的过敏原驱动的有限稀释分析。

DOI:
10.1093/intimm/8.6.897
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发表时间:
1996
影响因子:
4.4
通讯作者:
K. HayGlass
K. HayGlass
中科院分区:
医学3区
文献类型:
--
作者:
Y. Li;F. Simons;F. Jay;K. HayGlass

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在抗原驱动的原代培养中检测人IL-4合成的困难导致了对T细胞活化的较少生理方法的广泛依赖。虽然有一个Th 2样偏置的一般协议,细胞因子反应性的精确缺陷仍然存在争议。分析新鲜的,可移植的细胞群体响应同源的抗原驱动的刺激的细胞因子蛋白的产生仍然是一个重要的目标。在这里,有限稀释分析(LDA)被用来评估抗原刺激的细胞因子基因表达的新鲜外周血单核细胞(PBMC)。自然再免疫后1个月(当地草花粉季节的高峰),对来自19名草花粉敏感的过敏性鼻炎受试者和正常的非特应性对照的PBMC进行评价。令人惊讶的是,高度特应性受试者和临床上非过敏性个体表现出几乎相等的抗原特异性,CD 4依赖性细胞因子的生产,在短期培养与这些常见的环境抗原。正如预期的那样,Th 2样活性的显著增加在草花粉敏感个体的循环免疫库中是明显的,导致正常受试者中抗原刺激的IFN-γ:IL-4频率的中值比为117:1,而过敏性鼻炎受试者中为4:1(Mann-Whitney U检验,P = 0. 05)。00067)。这种Th 2样的偏向反映了在特应性供体的循环草花粉特异性库中,IFN-γ产生细胞的频率较低,而IL-4产生细胞的频率显著增加。每个特应性和正常受试者在抗原再刺激后产生IFN-γ(+/-IL-4)的观察结果表明,决定是否过敏或(临床)耐受性结果,不取决于遗传决定的能力,即过敏原反应性T细胞是否可以在任何给定个体中通过长期暴露于普遍存在的环境抗原而被刺激,而是取决于支配个体反应的细胞因子反应的性质。
Difficulties in detecting human IL-4 synthesis in antigen-driven primary culture have led to widespread reliance on less physiologic approaches to T cell activation. Although there is general agreement of a Th2-like bias, the precise defects in cytokine responsiveness remain controversial. Analysis of cytokine protein production by fresh, unselected cell populations in response to cognate, antigen-driven stimulation remains an important goal. Here, limiting dilution analysis (LDA) was used to evaluate antigen-stimulated cytokine gene expression by fresh peripheral blood mononuclear cells (PBMC). PBMC from 19 grass pollen sensitive, allergic rhinitis subjects and normal, non-atopic controls were evaluated 1 month after natural reimmunization (the peak of the local grass pollen season). Surprisingly, highly atopic subjects and clinically non-allergic individuals exhibited virtually equivalent antigen-specific, CD4-dependent cytokine production in response to short-term culture with these common environmental antigens. As anticipated, pronounced increases in Th2-like activity were evident in the circulating immune repertoire of grass pollen sensitive individuals, leading to a median ratio of antigen-stimulated IFN-gamma:IL-4 frequencies of 117:1 among normal subjects versus 4:1 among those with allergic rhinitis (Mann-Whitney U-test, P = 0. 00067). This Th2-like bias reflected both a lower frequency of IFN-gamma-producing cells and a markedly increased frequency of IL-4-producing cells in the circulating grass-pollen specific repertoire of atopic donors. The observation that every atopic and normal subject produced IFN-gamma (+/-IL-4) following antigen re-stimulation argues that the decision as to whether allergy or (clinical) tolerance results, hinges not on a genetically determined capacity of whether allergen-reactive T cells can be stimulated in any given individual by chronic exposure to ubiquitous environmental antigens, but on the nature of the cytokine response that comes to dominate that individual's response.
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期刊: SCIENCE
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作者:
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改变前列腺素 E2 对特应性皮炎细胞因子产生的调节。
DOI: --
发表时间: 1993
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Chan,SC;Kim,JW;HendersonJr,WR;Hanifin,JM
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DOI: 10.1016/0022-1759(91)90111-r
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DOI: --
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期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
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