HBV疫苗接种和HBV感染诱导HBV特异性自然杀伤细胞记忆

StephenW

Journal Summaries in Gastroenterology
HBV vaccination and HBV infection induces HBV-specific natural killer cell memory

Gut — Wijaya RS2, Read SA, Truong NR, et al. | April 01, 2020

The identification of antigen-specific memory natural killer cells (mNKs) in mice and non-human primates has challenged the view that vaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of the adaptive immune system. Researchers examined humans for the existence of HBV-specific mNKs after vaccination and in chronic HBV infection. Flow cytometry and ELISA were used to evaluate NK cell responses following challenge with HBV antigens in HBV vaccinated, non-vaccinated and chronic HBV-infected individuals. They observed higher cytotoxic and proliferative responses against autologous hepatitis B surface antigen (HBsAg)-pulsed monocyte-derived dendritic cells (moDCs) in NK cells from vaccinated subjects vs unvaccinated subjects. Moreover, significantly higher NK cell lysis of HBsAg-pulsed moDCs was observed relative to that of hepatitis B core antigen (HBcAg)-pulsed moDCs (non-vaccine antigen) or tumor necrosis factor α-activated moDCs in a NKG2D-dependent manner.  Further, greater degranulation against HBcAg-pulsed moDCs was observed in mNKs from chronic hepatitis B patients vs unvaccinated or vaccinated patients. Notably, there was a negative correlation of mNK activity with HBV DNA levels. Data suggest the existence of a mature mNKs following HBV antigen exposure either through vaccination or infection. For developing novel treatments targeting HBV in chronic infection, harnessing these antigen specific, functionally active mNKs provides an opportunity.

StephenW

胃肠病学杂志摘要
HBV疫苗接种和HBV感染诱导HBV特异性自然杀伤细胞记忆

肠道-Wijaya RS2，阅读SA，Truong NR等。 | 2020年4月1日

在小鼠和非人类灵长类动物中鉴定抗原特异性记忆自然杀伤细胞（mNKs）挑战了以下观点：针对乙型肝炎病毒（HBV）的疫苗接种可通过传统上被认为是适应性免疫域的免疫记忆赋予保护，使其免受随后的感染免疫系统。研究人员检查了人类在接种疫苗后以及慢性HBV感染中是否存在HBV特异性mNK。在接受HBV疫苗接种的，未接种疫苗的和慢性HBV感染的个体中，用HBV抗原攻击后，流式细胞仪和ELISA用于评估NK细胞反应。他们观察到接种疫苗的受试者与未接种疫苗的受试者相比，NK细胞对自体乙型肝炎表面抗原（HBsAg）脉冲单核细胞衍生的树突状细胞（moDC）具有更高的细胞毒性和增殖反应。此外，相对于乙肝核心抗原（HBcAg）脉冲的moDC（非疫苗抗原）或肿瘤坏死因子α激活的moDC，NKS2D依赖性的NK细胞裂解率明显高于HBsAg脉冲的moDC。此外，在慢性乙型肝炎患者与未接种疫苗或未接种疫苗的患者的mNKs中，观察到针对HBcAg脉冲的moDC的更大的脱粒作用。值得注意的是，mNK活性与HBV DNA水平呈负相关。数据表明，通过疫苗接种或感染暴露于HBV抗原后，存在成熟的mNKs。为了开发针对慢性感染中HBV的新疗法，利用这些抗原特异性，功能活跃的mNKs提供了机会。

StephenW

https://gut.bmj.com/content/earl ... l-2019-319252?rss=1