Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection.
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.
Chang
J Judy
JJ
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
Sirivichayakul
Sunee
S
Avihingsanon
Anchalee
A
Thompson
Alex J V
AJ
Revill
Peter
P
Iser
David
D
Slavin
John
J
Buranapraditkun
Supranee
S
Marks
Pip
P
Matthews
Gail
G
Cooper
David A
DA
Kent
Stephen J
SJ
Cameron
Paul U
PU
Sasadeusz
Joe
J
Desmond
Paul
P
Locarnini
Stephen
S
Dore
Gregory J
GJ
Ruxrungtham
Kiat
K
Lewin
Sharon R
SR
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
D016207:Cytokines; D006513:Hepatitis B e Antigens