Institute of Liver and Biliary Sciences, New Delhi, India; Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
J Viral Hepat. 2013 Aug;20(8):582-91. doi: 10.1111/jvh.12078. Epub 2013 Feb 14.
Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.
乙型肝炎病毒(HBV)在婴儿期或幼儿期感染会导致高比例的持续性感染(25-90%)。垂直获得性 HBV 感染中病毒持续存在的高比率的免疫学基础尚未完全阐明。CD8 T 细胞在清除成人乙型肝炎病毒感染中起着关键作用。在此,我们试图描绘 T 细胞在 HBsAg+ve 新生儿病毒持续存在中的作用。在出生时,对 HBsAg+ve(N=12)、HBsAg-ve(N=10)和健康新生儿(HC:N=15)的外周血和脐带血进行流式细胞术评估 T 细胞频率和功能。在所有三组中,未观察到 CD8 和 CD4 T 细胞的频率存在显著差异。然而,与 HBsAg-ve(28.12%)和 HC(11.06%)相比,HBsAg+ve 中 FoxP3 表达调节性 T 细胞的频率显著更高(63.79%)(P<0.05)。此外,与 HBsAg-ve 和 HC 相比,HBsAg+ve 新生儿的 CD8 T 细胞产生 IFN-γ和表达 CD107A(细胞毒性能力)的功能缺陷,与 TCRζ-链表达的 CD8 T 细胞减少呈正相关(r(2)>0.93,P<0.05)。尽管三组的 CD8 T 细胞频率相等,但 HBsAg+ve 新生儿的 CD8 T 细胞功能失调。调节性 T 细胞的扩增和 TCR 信号受损可能代表适应性免疫系统对慢性 HBV 感染的免疫耐受状态。