TY - JOUR
T1 - Immunopathogenesis of hepatitis B persistent infection
T2 - Implications for immunotherapeutic strategies
AU - Kondo, Yasuteru
AU - Ueno, Yoshiyuki
AU - Shimosegawa, Tooru
N1 - Funding Information:
Acknowledgment This work was supported in part from Health and Labour Sciences Research Grants for the Research on Measures for Intractable Diseases (from the Ministry of Health, Labour and Welfare of Japan).
PY - 2009/4
Y1 - 2009/4
N2 - It has been shown that cellular immunity, especially by cytotoxic T lymphocytes (CTLs), NK cells and NK-T cells, plays a central role in the control of virus infection. In addition, CD4+ T cells facilitate both CTL and B-cell responses. Hyporesponsiveness of HBV-specific T cells in peripheral blood has been shown in patients with chronic HBV infection. Interferon and nucleos(t)ide analogs, such as lamivudine, adefovir, entecavir and tenofovir, are the currently available treatments. Unfortunately, the efficacy of nucleos(t)ide analogs is limited by viral reactivation by the emergence of escaped mutants in cases of prolonged treatment. Therefore, immunotherapy is one of the significant options to eradicate or control HBV replication without drugs. The aim of immunotherapies is to decrease the levels of viral replication and to eradicate infected hepatocytes. For this reason, new strategies for immunotherapies by vaccination target not only the induction or stimulation of CD4+ and CD8+ T cell responses, but also the induction of proinflammatory cytokines capable of controlling viral replication. We will review the immunopathogenesis of persistent HBV infection, especially focusing on the mechanisms of immune suppression. Then we will review the immunotherapy for HBV persistent infection.
AB - It has been shown that cellular immunity, especially by cytotoxic T lymphocytes (CTLs), NK cells and NK-T cells, plays a central role in the control of virus infection. In addition, CD4+ T cells facilitate both CTL and B-cell responses. Hyporesponsiveness of HBV-specific T cells in peripheral blood has been shown in patients with chronic HBV infection. Interferon and nucleos(t)ide analogs, such as lamivudine, adefovir, entecavir and tenofovir, are the currently available treatments. Unfortunately, the efficacy of nucleos(t)ide analogs is limited by viral reactivation by the emergence of escaped mutants in cases of prolonged treatment. Therefore, immunotherapy is one of the significant options to eradicate or control HBV replication without drugs. The aim of immunotherapies is to decrease the levels of viral replication and to eradicate infected hepatocytes. For this reason, new strategies for immunotherapies by vaccination target not only the induction or stimulation of CD4+ and CD8+ T cell responses, but also the induction of proinflammatory cytokines capable of controlling viral replication. We will review the immunopathogenesis of persistent HBV infection, especially focusing on the mechanisms of immune suppression. Then we will review the immunotherapy for HBV persistent infection.
KW - CTL
KW - DC
KW - HBV
KW - Immunotherapy
KW - NK
KW - NK-T
KW - TLR
KW - Tregs
KW - Vaccine
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U2 - 10.1007/s12328-009-0074-z
DO - 10.1007/s12328-009-0074-z
M3 - Review article
AN - SCOPUS:67349281914
VL - 2
SP - 71
EP - 79
JO - Clinical Journal of Gastroenterology
JF - Clinical Journal of Gastroenterology
SN - 1865-7257
IS - 2
ER -