title: Circulating CD56dim natural killer cells and CD56+ T cells that produce interferon-γ or interleukin-10 are expanded in asymptomatic, E antigen-negative patients with persistent hepatitis B virus infection.
abstract: Infection with hepatitis B virus (HBV) can result in spontaneous resolution or chronic infection, which can remain asymptomatic or can progress to cirrhosis and/or hepatocellular carcinoma. The host immune response is thought to be a major determinant of the outcome of HBV infection and virus-specific cytotoxic T lymphocytes (CTL) can mediate immunity against the virus and cause liver pathology. Antigen-nonspecific innate lymphocytes may also contribute to HBV infection and liver disease, therefore, we examined the frequencies, phenotypes, cytolytic activities and cytokine profiles of circulating natural killer (NK) cells, CD1d-restricted invariant natural killer T (iNKT) cells and CD56(+) T cells in 102 asymptomatic HBV-infected patients and compared them with those in 66 uninfected control subjects. NK cells expressing low levels of CD56 (CD56(dim)) and CD56(+) T cells were significantly expanded in the circulation of HBV-infected patients compared with control subjects. CD1d expression and iNKT cell frequencies were similar in both groups. Despite these expansions, we did not detect augmented natural or cytokine-induced cytotoxicity in the HBV-infected subjects. All lymphocyte populations studied produced interferon-γ (IFN-γ) significantly more frequently when taken from HBV-infected patients compared with when taken from healthy controls. Additionally, NK cells from the patients more frequently produced interleukin-10. As our HBV-infected cohort consisted of asymptomatic patients with low viral loads, we propose that CD56(dim) NK cells and CD56(+) T cells control HBV infection by noncytolytic mechanisms.
authors.affiliation: Department of Immunology, School of Medicine, Trinity College, Dublin 2, Ireland; Institute of Immunology, National University of Ireland, Maynooth, Ireland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Conroy
authors.forename: R
authors.initials: R
authors.lastname: Mac Nicholas
authors.forename: R
authors.initials: R
authors.lastname: Grealy
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: J A
authors.initials: JA
authors.lastname: Otegbayo
authors.forename: S
authors.initials: S
authors.lastname: O'Dea
authors.forename: F
authors.initials: F
authors.lastname: Mulcahy
authors.forename: T
authors.initials: T
authors.lastname: Ryan
authors.forename: S
authors.initials: S
authors.lastname: Norris
authors.forename: D G
authors.initials: DG
authors.lastname: Doherty
mesh_terms: D000293:Adolescent; D000328:Adult; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism; D058070:Asymptomatic Diseases; D019002:CD56 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D005006:Ethnicity; D005260:Female; D015870:Gene Expression; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D055610:Antigens, CD1d; D019002:CD56 Antigen; D006513:Hepatitis B e Antigens; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: cytokines; cytotoxicity; hepatitis B; natural killer; natural killer T