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Publication : Overcoming tolerance in hepatitis B virus transgenic mice: a possible involvement of regulatory T cells.

First Author  Roh S Year  2003
Journal  Microbiol Immunol Volume  47
Issue  6 Pages  453-60
PubMed ID  12906106 Mgi Jnum  J:127655
Mgi Id  MGI:3764577 Doi  10.1111/j.1348-0421.2003.tb03370.x
Citation  Roh S, et al. (2003) Overcoming tolerance in hepatitis B virus transgenic mice: a possible involvement of regulatory T cells. Microbiol Immunol 47(6):453-60
abstractText  The hepatitis B virus (HBV) transgenic mouse (Tg) 50-4 strain is immunologically tolerant to HBV antigens. Various vaccination strategies have been attempted but failed to break the tolerance in the mouse. Although the tolerance to HBV antigen is maintained, this mouse strain develops spontaneous liver disease beginning at the age of about 3 months. We attempted to induce immune responses to HBV surface antigen (HBsAg) in the Tg by immunization with recombinant vaccinia virus expressing HBsAg (vvHBV), and observed different immunological responsiveness between 2-month-old and 5-month-old Tg. In contrast to the unbreakable tolerance reported previously, we could induce both the cytotoxic T lymphocyte (CTL) and the antibody response against HBsAg by the vvHBV immunization. The cytokine expression pattern indicated that T helper 1 type immune response was induced. However, interestingly, these immune responses were observed only in the 5-month-old Tg, but not in the 2-month-old Tg. Furthermore, CD4+ T cells from 2-month-old mice, but not those from 5-month-old mice, inhibited CTL response to HBV antigen when adoptively transferred to C57BL/6. These results suggest the possible involvement of regulatory T cell function in the HBV Tg for maintaining tolerance. This study would contribute to a better understanding of immune status of the HBV Tg as a model of human chronic hepatitis and to the search for new therapeutic targets for chronic viral infections.
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