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不同的Bla-g T细胞抗原在哮喘患者和鼻炎患者的免疫反应中占主导地位。

Different Bla-g T cell antigens dominate responses in asthma versus rhinitis subjects.

作者信息

Dillon M B C, Schulten V, Oseroff C, Paul S, Dullanty L M, Frazier A, Belles X, Piulachs M D, Visness C, Bacharier L, Bloomberg G R, Busse P, Sidney J, Peters B, Sette A

机构信息

La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.

Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.

出版信息

Clin Exp Allergy. 2015 Dec;45(12):1856-67. doi: 10.1111/cea.12643.

Abstract

BACKGROUND AND OBJECTIVE

The allergenicity of several German cockroach (Bla-g) antigens at the level of IgE responses is well established. However, less is known about the specificity of CD4+ TH responses, and whether differences exist in associated magnitude or cytokine profiles as a function of disease severity.

METHODS

Proteomic and transcriptomic techniques were used to identify novel antigens recognized by allergen-specific T cells. To characterize different TH functionalities of allergen-specific T cells, ELISPOT assays with sets of overlapping peptides covering the sequences of known allergens and novel antigens were employed to measure release of IL-5, IFNγ, IL-10, IL-17 and IL-21.

RESULTS

Using these techniques, we characterized TH responses in a cohort of adult Bla-g-sensitized subjects, either with (n = 55) or without (n = 17) asthma, and nonsensitized controls (n = 20). T cell responses were detected for ten known Bla-g allergens and an additional ten novel Bla-g antigens, representing in total a 5-fold increase in the number of antigens demonstrated to be targeted by allergen-specific T cells. Responses of sensitized individuals regardless of asthma status were predominantly TH 2, but higher in patients with diagnosed asthma. In asthmatic subjects, Bla-g 5, 9 and 11 were immunodominant, while, in contrast, nonasthmatic-sensitized subjects responded mostly to Bla-g 5 and 4 and the novel antigen NBGA5.

CONCLUSIONS

Asthmatic and nonasthmatic cockroach-sensitized individuals exhibit similar TH 2-polarized responses. Compared with nonasthmatics, however, asthmatic individuals have responses of higher magnitude and different allergen specificity.

摘要

背景与目的

几种德国小蠊(Bla-g)抗原在IgE反应水平的致敏性已得到充分证实。然而,关于CD4+ TH反应的特异性,以及作为疾病严重程度函数的相关强度或细胞因子谱是否存在差异,人们了解较少。

方法

采用蛋白质组学和转录组学技术鉴定过敏原特异性T细胞识别的新抗原。为了表征过敏原特异性T细胞的不同TH功能,使用覆盖已知过敏原和新抗原序列的重叠肽组进行ELISPOT分析,以测量IL-5、IFNγ、IL-10、IL-17和IL-21的释放。

结果

使用这些技术,我们对一组成年Bla-g致敏受试者的TH反应进行了表征,其中有哮喘的受试者(n = 55)、无哮喘的受试者(n = 17)以及未致敏的对照组(n = 20)。检测到针对十种已知Bla-g过敏原和另外十种新的Bla-g抗原的T细胞反应,这表明过敏原特异性T细胞靶向的抗原数量总共增加了5倍。无论哮喘状态如何,致敏个体的反应主要是TH2型,但在诊断为哮喘的患者中反应更高。在哮喘患者中,Bla-g 5、9和11是免疫显性的,而相比之下,未患哮喘的致敏个体主要对Bla-g 5和4以及新抗原NBGA5有反应。

结论

哮喘和未患哮喘的蟑螂致敏个体表现出相似的TH2极化反应。然而,与未患哮喘的个体相比,哮喘个体的反应强度更高且过敏原特异性不同。

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