PD-1/PDL1 and CD28/CD80 pathways modulate natural killer T cell function to inhibit hepatitis B virus replication

Summary α‐Galactosylceramide (α‐GalCer)‐activated natural killer T (NKT) cells have antiviral properties against hepatitis B virus (HBV). However, α‐GalCer activation of NKT cells can induce anergy. We hypothesized that this effect may be overcome by a treatment strategy that includes manipulation o...

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Veröffentlicht in:	Journal of viral hepatitis 2013-04, Vol.20 (s1), p.27-39
Hauptverfasser:	Wang, X. F., Lei, Y., Chen, M., Chen, C. B., Ren, H., Shi, T. D.
Format:	Artikel
Sprache:	eng
Schlagworte:	Anergy Animal models Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - immunology Antiviral activity B7-1 Antigen - immunology B7-1 Antigen - metabolism B7-H1 Antigen - immunology B7-H1 Antigen - metabolism CD28 antigen CD28 Antigens - immunology CD28 Antigens - metabolism CD28/CD80 CD80 antigen Cell culture China Chronic infection Disease Models, Animal Female Flow Cytometry galactosylceramide Galactosylceramides - administration & dosage Galactosylceramides - immunology Galactosylceramides - pharmacology gamma -Interferon Hepatitis B virus Hepatitis B virus - drug effects Hepatitis B virus - genetics Hepatitis B virus - physiology Hepatitis B, Chronic - drug therapy Hepatitis B, Chronic - immunology Hepatitis B, Chronic - virology Humans Immunomodulation Injuries Interferon Interleukins Leukocytes (mononuclear) Liver Lymphocyte Activation Lymphocytes T Mice Mice, Inbred C57BL Mice, Transgenic Monoclonal antibodies Natural killer cells natural killer T cell Natural Killer T-Cells - immunology Natural Killer T-Cells - metabolism PD-1 protein PD1/PDL1 Programmed Cell Death 1 Receptor - immunology Programmed Cell Death 1 Receptor - metabolism Receptors, Immunologic - immunology Receptors, Immunologic - metabolism Replication Transgenic mice Treatment Outcome Virus Replication - immunology
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Zusammenfassung:	Summary α‐Galactosylceramide (α‐GalCer)‐activated natural killer T (NKT) cells have antiviral properties against hepatitis B virus (HBV). However, α‐GalCer activation of NKT cells can induce anergy. We hypothesized that this effect may be overcome by a treatment strategy that includes manipulation of CD28/CD80 costimulatory and PD‐1/PDL1 coinhibitory signals of NKT cells, thereby enhancing the anti‐HBV effect of α‐GalCer. We established a transgenic mouse model of chronic HBV infection and investigated hepatic NKT cell frequencies, functions and expression of immunomodulatory factors. Our results showed that compared with uninfected control mice, hepatic NKT cells from HBV transgenic mice displayed lower frequencies (7.91% vs 16.74%, P
ISSN:	1352-0504 1365-2893
DOI:	10.1111/jvh.12061