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变应原特异性幼稚和记忆 CD4+ T 细胞在过敏和非过敏个体之间表现出功能和表型的差异。

Allergen-specific naïve and memory CD4+ T cells exhibit functional and phenotypic differences between individuals with or without allergy.

机构信息

Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.

出版信息

Eur J Immunol. 2010 Sep;40(9):2460-9. doi: 10.1002/eji.201040328.

DOI:10.1002/eji.201040328
PMID:20690179
Abstract

Although allergen-specific CD4(+) T cells are detectable in the peripheral blood of both individuals with or without allergy, their frequencies and phenotypes within the memory as well as naïve repertoires are incompletely known. Here, we analyzed the DRB1*0401-restricted responses of peripheral blood-derived memory (CD4(+)CD45RO(+)) and naïve (CD4(+)CD45RA(+)) T cells from subjects with or without allergy against the immunodominant epitope of the major cow dander allergen Bos d 2 by HLA class II tetramers in vitro. The frequency of Bos d 2(127-142)-specific memory T cells in the peripheral blood-derived cultures appeared to be higher in subjects with allergy than those without, whereas naïve Bos d 2(127-142)-specific T cells were detectable in the cultures of both groups at nearly the same frequency. Surprisingly, the TCR avidity of Bos d 2(127-142)-specific T cells of naïve origin, as assessed by the intensity of HLA class II tetramer staining, was found to be higher in individuals with allergy. Upon restimulation, long-term Bos d 2(127-142)-specific T-cell lines generated from both memory and naïve T-cell pools from individuals with allergy proliferated more strongly, produced more IL-4 and IL-10, and expressed higher levels of CD25 but lower levels of CXCR3 than the T-cell lines from individuals without allergy, demonstrating differences also at the functional level. Collectively, our current results suggest that not only the memory but also the naïve allergen-specific T-cell repertoires differ between individuals with or without allergy.

摘要

虽然过敏个体和非过敏个体的外周血中均可检测到过敏原特异性 CD4(+)T 细胞,但它们在记忆和幼稚 T 细胞库中的频率和表型尚不完全清楚。在此,我们通过 HLA Ⅱ类四聚体分析了过敏个体和非过敏个体外周血来源的记忆(CD4(+)CD45RO(+))和幼稚(CD4(+)CD45RA(+))T 细胞对主要牛过敏原 Bos d 2 的免疫优势表位的 DRB1*0401 限制性反应。与非过敏个体相比,过敏个体外周血来源的培养物中 Bos d 2(127-142)-特异性记忆 T 细胞的频率似乎更高,而两组的培养物中均可检测到几乎相同频率的幼稚 Bos d 2(127-142)-特异性 T 细胞。令人惊讶的是,通过 HLA Ⅱ类四聚体染色强度评估,幼稚来源的 Bos d 2(127-142)-特异性 T 细胞的 TCR 亲和力在过敏个体中更高。在重新刺激后,从过敏个体的记忆和幼稚 T 细胞库中产生的长期 Bos d 2(127-142)-特异性 T 细胞系增殖更强烈,产生更多的 IL-4 和 IL-10,并表达更高水平的 CD25,但 CXCR3 水平较低,表明在功能水平上也存在差异。总的来说,我们目前的结果表明,不仅是记忆 T 细胞,而且幼稚的过敏原特异性 T 细胞库在过敏个体和非过敏个体之间存在差异。

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