Pegylated Interferon-ɑ (IFN-ɑ) Enhances the Inhibitory Effect of Natural Killer Cells on Regulatory T Cells via IFN-γ in Chronic Hepatitis B.

Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE

Publication: Jan. 2011- : Oxford : Oxford University Press
Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press

T-Lymphocytes, Regulatory*; Antiviral Agents/*therapeutic use ; Hepatitis B Surface Antigens/*immunology ; Hepatitis B, Chronic/*drug therapy ; Hepatitis B, Chronic/*immunology ; Interferon-alpha/*pharmacology ; Killer Cells, Natural/*drug effects ; Killer Cells, Natural/*immunology ; Polyethylene Glycols/*pharmacology; Animals ; Hepatitis B Surface Antigens/therapeutic use ; Hepatitis B virus ; Hepatitis B, Chronic/virology ; Humans ; Interferon-alpha/therapeutic use ; Interferon-gamma ; Killer Cells, Natural/metabolism ; Mice ; Polyethylene Glycols/therapeutic use ; Treatment Outcome

The immunomodulatory role of natural killer (NK) cells has been recognized recently, but its effects on CD4+CD25+ regulatory T cells (Tregs) during chronic hepatitis B (CHB) infection and treatment remain unclear. A total of 116 nucleos(t)ide analogue (NA)-treated CHB patients were included. An inverse correlation between the peripheral frequencies of NK cells and Tregs was found in NA suppressed patients following pegylated interferon-ɑ (PegIFN-ɑ)-based treatment. Furthermore, NK cells suppressed the proliferation and differentiation of Tregs through secreting IFN-γ as was evidenced in the circulation of NA-treated CHB patients as well as in liver of HBV-carrier mouse model. Additionally, the inhibition could be enhanced by PegIFN-ɑ treatment, which was correlated to more vigorous HBV-specific T-cell responses and marked reduction in HBsAg. Our study reveals a novel immunomodulatory mechanism of NK cells and provides a theoretical basis for PegIFN-ɑ as an immunotherapy agent in treating patients with CHB.
(© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].)

Keywords: IFN-γ; chronic hepatitis B; immune regulation; natural killer cells; regulatory T cells

0 (Antiviral Agents)
0 (Hepatitis B Surface Antigens)
0 (Interferon-alpha)
3WJQ0SDW1A (Polyethylene Glycols)
82115-62-6 (Interferon-gamma)

Date Created: 20210419 Date Completed: 20220202 Latest Revision: 20220202

20240829

10.1093/infdis/jiab216

33870432