Back to Search
Start Over
HBV vaccination and HBV infection induces HBV-specific natural killer cell memory
- Source :
- Gut. :gutjnl-2019
- Publication Year :
- 2020
- Publisher :
- BMJ, 2020.
-
Abstract
- ObjectiveVaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of the adaptive immune system. This view has been challenged following the identification of antigen-specific memory natural killer cells (mNKs) in mice and non-human primates. While the presence of mNKs has been suggested in humans based on the expansion of NK cells following pathogen exposure, evidence regarding antigen-specificity is lacking. Here, we demonstrate the existence of HBV-specific mNKs in humans after vaccination and in chronic HBV infection.DesignNK cell responses were evaluated by flow cytometry and ELISA following challenge with HBV antigens in HBV vaccinated, non-vaccinated and chronic HBV-infected individuals.ResultsNK cells from vaccinated subjects demonstrated higher cytotoxic and proliferative responses against autologous hepatitis B surface antigen (HBsAg)-pulsed monocyte-derived dendritic cells (moDCs) compared with unvaccinated subjects. Moreover, NK cell lysis of HBsAg-pulsed moDCs was significantly higher than that of hepatitis B core antigen (HBcAg)-pulsed moDCs (non-vaccine antigen) or tumour necrosis factor α-activated moDCs in a NKG2D-dependent manner. The mNKs response was mediated by CD56dim NK cells coexpressing CD57, CD69 and KLRG1. Further, mNKs from chronic hepatitis B patients exhibited greater degranulation against HBcAg-pulsed moDCs compared with unvaccinated or vaccinated patients. Notably, mNK activity was negatively correlated with HBV DNA levels.ConclusionsOur data support the presence of a mature mNKs following HBV antigen exposure either through vaccination or infection. Harnessing these antigen specific, functionally active mNKs provides an opportunity to develop novel treatments targeting HBV in chronic infection.
- Subjects :
- 0301 basic medicine
Hepatitis B virus
HBsAg
business.industry
Gastroenterology
Hepatitis B
Acquired immune system
medicine.disease
medicine.disease_cause
Natural killer cell
03 medical and health sciences
HBcAg
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Immune system
Antigen
Immunology
medicine
030211 gastroenterology & hepatology
business
Subjects
Details
- ISSN :
- 14683288 and 00175749
- Database :
- OpenAIRE
- Journal :
- Gut
- Accession number :
- edsair.doi...........f9476a12341739ac0a874fbd02d98bad