Dynamic changes of CTL, NK, NKT cells in acute Hepatitis B

StephenW

http://www.virologyj.com/content/pdf/1743-422X-8-199.pdf
Dynamic changes of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and natural killer T (NKT) cells in patients with acute hepatitis B infection
Jun Li1,2*†, Yaping Han1†, Ke Jin1, Yufeng Wan1, Shixia Wang2,3, Bo Liu1, Yuan Liu1, Shan Lu2,3 and Zuhu Huang1,2*
* Correspondence: [email protected]; [email protected]
† Contributed equally
1Department of Infectious Diseases, The First Affiliated Hospital with Nanjing
Medical University, Nanjing 210029, China
Full list of author information is available at the end of the article
Abstract
Background:
The goal of this study is to observe changes in HBcAg-specific cytotoxic T lymphocytes (CTLs), natural killer (NK) and natural killer T (NKT) cells from peripheral blood and to relate such changes on viral clearance and liver injury in patients with acute hepatitis B (AHB).
Methods:
Dynamic profiles on the frequency of HLA-A0201-restricted HBcAg18-27 pentamer complex (MHCPentamer)-specific CTLs and lymphocyte subsets in AHB patients were analyzed in addition to liver function tests, HBV serological markers, and HBV DNA levels. ELISPOT was used to detect interferon-gamma (INF-g) secretion in specific CTLs stimulated with known T cell epitope peptides associated with HBV surface protein, polymerase, and core protein.
Results:
HBV-specific CTL frequencies in AHB patients were much higher than in patients with chronic hepatitis B (CHB) (p < 0.05). HBeAg and HBV DNA disappeared earlier in AHB patients with a high frequency of HBV-specific CTLs compared with those with a low frequency of HBV-specific CTLs (p = 0.001 and 0.024, respectively). INF-gspots of effector cells stimulated by Pol575-583, Env348-357, or Core18-27 epitope peptides were significantly greater in AHB patients than in CHB patients (p < 0.01). CD3+CD8+ T cell numbers in AHB patients was more than observed in the healthy control group from the first to the fourth week after admission (p = 0.008 and 0.01, respectively); the number of CD3+CD8+ T cells and frequency of HBcAg18-27-specific CTLs in AHB patients reached
peak levels at the second week after admission. NK and NKT cell numbers were negatively correlated with the frequency of HBcAg-specific CTLs (r = -0.266, p = 0.05).
Conclusions:
Patients with AHB possess a higher frequency of HBcAg-specific CTLs than CHB patients. The frequency of specific CTLs in AHB patients is correlated with HBeAg clearance indicating that HBV-specific CTLs play an important role in viral clearance and the self-limited process of the disease. Furthermore, NK and NKT cells are likely involved in the early, non-specific immune response to clear the virus.




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StephenW

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摘要
背景：这项研究的目的是观察HBcAg特异性细胞毒性T淋巴细胞（CTL）的变化，
自然杀伤（NK）和自然杀伤T（NKT）从外周血细胞和病毒与这种变化
患者在急性乙型肝炎（AHB）的清除和肝脏损伤。
方法：HLA - A020​​1限制HBcAg18 - 27五聚体复合物（MHCPentamer）的频率的动态配置文件 -
特异性CTL和AHB患者的淋巴细胞亚群进行了分析，除了肝功能检查，
乙肝病毒血清学标志和HBV DNA水平。酶联免疫斑点法用于检测γ-干扰素（INF - G）分泌
刺激特异性CTL与著名的T细胞表位肽与乙肝病毒的表面蛋白，聚合酶关联，
核心蛋白。
结果：AHB患者HBV特异性CTL频率比慢性乙型肝炎患者高得多
（HBV）（P <0.05）。 HBeAg和HBV DNA消失在AHB患者的HBV特异性的高频率
CTL的比较与HBV特异性CTL的低频率（P = 0.001和0.024，分别）。 INF - G
Pol575 - 583 - 357 Env348，或Core18 - 27抗原表位肽刺激的效应细胞的斑点均显着
在AHB患者大于慢性乙型肝炎患者（P <0.01）。 CD3 + CD8 + AHB患者的T细胞数目超过
在健康对照组从第一个观察到入学后的第四周（P = 0.008和0.01，
分别）; CD3 + CD8 + T细胞和HBcAg18 - 27 -特异性CTL的频率在AHB患者的人数达到
在入院后的第二个星期的最高水平。 NK细胞和NKT细胞数呈负相关
HBcAg特异性的CTL（R = -0.266，P = 0.05）的频率。
结论：与AHB患者具有较高的比例慢性乙型肝炎患者HBcAg特异性CTL的频率。 “
AHB患者特异性CTL的频率与HBeAg的指示间隙，HBV特异性CTL
在病毒清除和疾病的自限的过程中发挥的重要作用。此外，NK细胞和NKT细胞
在早期的非特异性免疫反应清除病毒有可能参与。