Antiviral CD8-mediated responses in chronic HCV carriers with HBV superinfection.
Hepatitis B virus (HBV) superinfection in chronic hepatitis C represents a natural model to investigate whether or not hepatitis C virus (HCV) can influence priming and maturation of antiviral T cells; whether or not HBV superinfection, which is known to determine control of HCV replication, can restore HCV-specific T cell responsiveness; and whether or not cytokines stimulated by HBV infection can contribute to HCV control. To address these issues, the function of CD8 cells specific for HBV and HCV was studied longitudinally in two chronic HCV patients superinfected with HBV. Patients with acute hepatitis B were also examined. Frequency and function of HBV tetramer+ CD8 cells were comparable in patients acutely infected with HBV with or without chronic HCV infection. HBV-specific CD8 cell function was efficiently expressed irrespective of serum HCV-RNA levels. Moreover, fluctuations of HCV viremia at the time of HBV superinfection were not associated with evident changes of CD8 responsiveness to HCV. Finally, no correlation was found between serum levels of interferon alpha, interleukin (IL)-12, IL-10, or IL-18 and control of HCV replication. In conclusion, HCV did not affect the induction of primary and memory HBV-specific CD8 responses. HCV-specific CD8 responses were undetectable when HCV-RNA was negative, showing that inhibition of HCV replication in the setting of a HBV superinfection was not sufficient to induce a restoration of CD8 reactivity against HCV.
Boni
Carolina
C
Divisione Malattie Infettive ed Epatologia (Division of Infectious Diseases and Hepatology), Azienda Ospedaliera Universitaria di Parma, Parma, Italy.
Amadei
Barbara
B
Urbani
Simona
S
Fisicaro
Paola
P
Zerbini
Alessandro
A
Mori
Cristina
C
Missale
Gabriele
G
Bertoni
Roberto
R
Azzurri
Annalisa
A
Del Prete
Gianfranco
G
Ferrari
Carlo
C
D000998:Antiviral Agents / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002353:Carrier State; D016207:Cytokines / Q000097:blood; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D007109:Immunity; D008137:Longitudinal Studies; D010455:Peptides / Q000235:genetics / Q000276:immunology; D015163:Superinfection / Q000276:immunology*; D014779:Virus Replication
D000998:Antiviral Agents; D016827:CD8 Antigens; D016207:Cytokines; D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides