活动性肺结核或潜伏性结核感染患者外周血T细胞库中T细胞受体β可变区的分子特征分析。
Molecular characterization of T cell receptor beta variable in the peripheral blood T cell repertoire in subjects with active tuberculosis or latent tuberculosis infection.
作者信息
Yang Jiezuan, He Jianqin, Huang Haijun, Ji Zhongkang, Wei Li, Ye Ping, Xu Kaijin, Li Lanjuan
机构信息
State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
出版信息
BMC Infect Dis. 2013 Sep 8;13:423. doi: 10.1186/1471-2334-13-423.
BACKGROUND
T cells are closely linked to the clinical manifestations of subjects with Mycobacterium tuberculosis (MTB) infection. T cell receptor beta variable (TCRBV) is a signal and indicative molecule on the membrane of T lymphocytes, reflecting the composition and specificity of T cells. The molecular profiles of TCRBV in peripheral blood mononuclear cells (PBMCs) and their subpopulations (CD4+ and CD8+ T cells) from subjects with active tuberculosis (TB) or latent TB infection (LTBI) have not been well described.
METHODS
In 42 subjects with active TB or LTBI, PMBCs and their subsets were separated and sorted. The molecular profiles of the TCRBV complementarity determining region 3 (CDR3) in the three cell populations were investigated using our recently developed gene melting spectral pattern (GMSP) assay. The TCRBV members were then cloned and sequenced when their GMSP image profiles showed a single-peak.
RESULTS
The average number of skewed TCRBV molecules in the CD4+ cell subset was significantly higher than that in PBMCs and CD8+ T cells. TCRBV12, BV13.1, BV13.2, and BV24 were expressed more prevalently than other TCRBV gene families in the three cell populations. In addition, relatively conserved amino acid motifs were identified in TCRBV5.1 and BV20 CDR3 in PBMCs and its subsets. The monoclonal TCRBV14 and BV23 expressed were different between active TB and LTBI subjects.
CONCLUSIONS
These results indicate that the T cell immune response is complex and multi-specific in active TB and LTBI subjects. Analysis of TCRBV expression in CD4+ T cells suggest that it could be useful in assessing the composition and status of circulating T cells. Furthermore, the expression of TCRBV14, BV23 and the sequencing of CDR3 amino acid motifs of TCRBV5.1, BV20 could be used in the differential diagnosis and treatment of subjects with active TB or LTBI.
背景
T细胞与结核分枝杆菌（MTB）感染患者的临床表现密切相关。T细胞受体β可变区（TCRBV）是T淋巴细胞膜上的一种信号和指示分子，反映T细胞的组成和特异性。活动性结核病（TB）或潜伏性结核感染（LTBI）患者外周血单个核细胞（PBMC）及其亚群（CD4+和CD8+ T细胞）中TCRBV的分子特征尚未得到充分描述。
方法
在42例活动性TB或LTBI患者中，分离并分选PBMC及其亚群。使用我们最近开发的基因熔解光谱模式（GMSP）分析法研究三个细胞群体中TCRBV互补决定区3（CDR3）的分子特征。当TCRBV成员的GMSP图像谱显示为单峰时，对其进行克隆和测序。
结果
CD4+细胞亚群中TCRBV分子偏斜的平均数量显著高于PBMC和CD8+ T细胞。在三个细胞群体中，TCRBV12、BV13.1、BV13.2和BV24的表达比其他TCRBV基因家族更为普遍。此外，在PBMC及其亚群的TCRBV5.1和BV20 CDR3中鉴定出相对保守的氨基酸基序。活动性TB和LTBI患者中表达的单克隆TCRBV14和BV23不同。
结论
这些结果表明，活动性TB和LTBI患者的T细胞免疫反应是复杂的且具有多特异性。对CD4+ T细胞中TCRBV表达的分析表明，它可能有助于评估循环T细胞的组成和状态。此外，TCRBV14、BV23的表达以及TCRBV5.1、BV20的CDR3氨基酸基序测序可用于活动性TB或LTBI患者的鉴别诊断和治疗。
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