Yang Jiezuan, Chen Jiajia, Mao Hejun, Yi Ping, Yan Dong, He Jianqin, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
FEMS Immunol Med Microbiol. 2012 Aug;65(3):448-55. doi: 10.1111/j.1574-695X.2012.00969.x. Epub 2012 May 21.
This study aimed to determine the degree of clonal expansion of T cells in peripheral blood mononuclear cells (PBMCs) isolated from patients suffering from different clinical types of hepatitis B (HB) infection and to analyse the clinical relevance of the skewed T-cell receptor beta variable (TCRBV). Sera and PBMCs were collected from 90 HB patients. Gene melting spectral pattern (GMSP) analysis was used to determine the distribution and expansion of populations expressing specific TCRBV complementary determined region 3 (CDR3) genes. TCRBV genes associated with monoclonal expansion were sequenced. TCRBV families from the majority of patients (80/90) displayed skewed T-cell expansion. Furthermore, TCRBV11, BV12 and BV13.1 were more frequent than other TCRBV genes; the sequence of TCRBV11 CDR3 was expressed as 'VYNEQ' in all patients and was accompanied by the BJ2.1 fragment. In patients with chronic HB, the frequency of skewed TCRBV was inversely correlated with hepatitis B virus (HBV) DNA levels. The persistently skewed TCRBV gene families in HB patients may be associated with the development and maintenance of hepatitis. GMSP analysis of TCRBV gene families may be helpful in estimating disease status, and BV11 may be associated with HBV replication in patients with chronic HBV infection.
本研究旨在确定从不同临床类型的乙型肝炎(HB)感染患者分离的外周血单个核细胞(PBMC)中T细胞的克隆扩增程度,并分析偏态T细胞受体β可变区(TCRBV)的临床相关性。收集了90例HB患者的血清和PBMC。采用基因熔解光谱模式(GMSP)分析来确定表达特定TCRBV互补决定区3(CDR3)基因的群体的分布和扩增情况。对与单克隆扩增相关的TCRBV基因进行测序。大多数患者(80/90)的TCRBV家族显示出偏态T细胞扩增。此外,TCRBV11、BV12和BV13.1比其他TCRBV基因更常见;TCRBV11 CDR3的序列在所有患者中均表达为“VYNEQ”,并伴有BJ2.1片段。在慢性HB患者中,偏态TCRBV的频率与乙型肝炎病毒(HBV)DNA水平呈负相关。HB患者中持续偏态的TCRBV基因家族可能与肝炎的发生和维持有关。对TCRBV基因家族进行GMSP分析可能有助于评估疾病状态,并且BV11可能与慢性HBV感染患者的HBV复制有关。