title: Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection.
abstract: Hepatitis B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+ T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+ T-cell count (P = 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+ T-cell count.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
authors.forename: J Judy
authors.initials: JJ
authors.lastname: Chang
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Alex J V
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Peter
authors.initials: P
authors.lastname: Revill
authors.forename: David
authors.initials: D
authors.lastname: Iser
authors.forename: John
authors.initials: J
authors.lastname: Slavin
authors.forename: Supranee
authors.initials: S
authors.lastname: Buranapraditkun
authors.forename: Pip
authors.initials: P
authors.lastname: Marks
authors.forename: Gail
authors.initials: G
authors.lastname: Matthews
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Joe
authors.initials: J
authors.lastname: Sasadeusz
authors.forename: Paul
authors.initials: P
authors.lastname: Desmond
authors.forename: Stephen
authors.initials: S
authors.lastname: Locarnini
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006509:Hepatitis B / Q000150:complications / Q000276:immunology* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D006513:Hepatitis B e Antigens