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针对丝虫抗原,特定TCRBV基因的选择性使用。

Selective usage of defined TCRBV genes in response to filarial antigens.

作者信息

Sartono E, van Eggermond M C, Kurniawan A, Maizels R M, van den Elsen P J, Yazdanbakhsh M

机构信息

Department of Parasitology, Leiden University, The Netherlands.

出版信息

Int Immunol. 1997 Jul;9(7):955-62. doi: 10.1093/intimm/9.7.955.

DOI:10.1093/intimm/9.7.955
PMID:9237104
Abstract

The characterization of T cell reactivities that are prone to down-modulation by filarial parasites is central to understanding how these nematodes can survive for long periods of time within their human host and to design appropriate immunoprophylactic measures. In the present study, TCRBV gene usage was analyzed in response to filarial antigens by PCR using a panel of TCRBV gene segment family-specific oligonucleotide primers. Analysis of individuals highly responsive to Brugia malayi adult worm antigen (BmA) (n = 4) indicated that following stimulation with BmA a maximum of four TCRBV gene families were over-represented in each subject. Those were TCRBV2, 9, 19 and 23 in subject 1; TCRBV8, 9 and 16 in subject 2; TCRBV2, 8, 9 and 11 in subject 3; and TCRBV13 and 23 in subject 4. The analysis of one subject who was unresponsive to BmA before but regained responsiveness after diethylcarbamazine treatment revealed that there was no overexpression of a particular TCRBV gene family before chemotherapy, whereas after chemotherapy three TCRBV gene families (TCRBV8, 16 and 19) were found to be overexpressed. Complementarity determining region 3 size analysis of a selection of the overexpressed TCRBV genes displayed oligoclonality in some of the observed expansions. Together these observations show that limited T cell subpopulations are clonally amplified in BmA-stimulated peripheral blood mononuclear cells of filarial responder subjects, possibly driven by a restricted number of antigens.

摘要

确定容易被丝虫寄生虫下调调节的T细胞反应性特征,对于理解这些线虫如何在人类宿主体内长期存活以及设计合适的免疫预防措施至关重要。在本研究中,使用一组TCRBV基因片段家族特异性寡核苷酸引物,通过PCR分析了对丝虫抗原反应时TCRBV基因的使用情况。对高度响应马来布鲁线虫成虫抗原(BmA)的个体(n = 4)进行分析表明,用BmA刺激后,每个受试者中最多有四个TCRBV基因家族过度表达。在受试者1中为TCRBV2、9、19和23;受试者2中为TCRBV8、9和16;受试者3中为TCRBV2、8、9和11;受试者4中为TCRBV13和23。对一名之前对BmA无反应但在乙胺嗪治疗后恢复反应性的受试者进行分析发现,化疗前没有特定TCRBV基因家族的过表达,而化疗后发现有三个TCRBV基因家族(TCRBV8、16和19)过表达。对一些过表达的TCRBV基因进行互补决定区3大小分析,发现在一些观察到的扩增中呈现寡克隆性。这些观察结果共同表明,在丝虫反应性受试者的BmA刺激外周血单核细胞中,有限的T细胞亚群发生克隆性扩增,可能由数量有限的抗原驱动。

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