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EFFECT OF HBV AND HCV COINFECTION ON ANTI-VIRAL T CELL RESPONSES
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C. Boni*, B. Amadei, S. Urbani, G. Elia, A. Cavalli, S. Cerioni, M. Malpeli,
G. Missale, C. Ferrari,
*Presenting Author
Department Of Infectious Diseases And Hepatology, Azienda Ospedaliera
Universitaria Di Parma, Parma, Italy
In HCV infection, HCV-specific CD8+ lymphocytes show various degrees of
impairment of antiviral function. To assess if this HCV-related impairment is
limited to HCV-specific T cells or can affect also cell-mediated immune
responses to other pathogens, we analyzed virus-specific T cell responses of
3 patients infected simultaneously with HCV and HBV (2 with chronic hepatitis
C and acute HBV infection who cleared successfully HBV but remained HCV-RNA
positive; one with simultaneous acute HBV and HCV infections who cleared HCV
but developed chronic hepatitis B) and 5 patients with acute HBV infection
alone, as controls. The cell-mediated immune response was studied with four
HLA A2/HCV-specific and six HLA-A2/HBV-specific tetramers. Frequencies and
perforin content of HBV- and HCV-specific T cells were analyzed ex-vivo,
while IFN-_ production, proliferation and cytolytic activity were analyzed
upon peptide stimulation.
The two patients with acute hepatitis B associated with chronic HCV infection
showed multispecific and strong HBV-specific cytotoxic T lymphocyte (CTL)
responses. The HCV-specific CTL response was only transient and weak although
HCV RNA dropped at low or undetectable levels at the time of HBV coinfection.
The third patient did not develop HBV-specific CTL responses but displayed a
strong and sustained HCV-specific CTL response.
In conclusion, the lack of effect of chronic HCV infection on the T
cell-response to another virus with tropism for the same organ suggests that
the HCV inhibitory effect is selective for HCV-specific T cell responses;
moreover, the immune response primed by HBV infection can only partially and
transiently control HCV infection.
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