Ongoing murine T1 or T2 immune responses to the hepatitis B surface antigen are excluded from the liver that expresses transgene-encoded hepatitis B surface antigen

Different protein- or DNA-based vaccination techniques are available that p rime potent humoral and cellular, T1 or T2 immune responses to the hepatiti s B surface Ag (HBsAg) in mice. T1 and T2 are immune responses with isotype profile indicating Th1 and Th2 immunoregulation, We tested whether HBsAg-s pecific immune responses can be established in transgenic mice that express HBsAg in the liver (HBs-tg mice) using either these different vaccination techniques or an adoptive transfer system. HBsAg-specific responses could n ot be primed in HBs-tg mice with the established, potent vaccine delivery t echniques. In contrast, adoptive transfers of T1- and T2-type HBsAg-immune spleen cells into congenic HBs-tg hosts (that were not conditioned by pretr eatment) suppressed HBsAg antigenemia and gave rise to HBsAg-specific serum Ab titers, The establishment of continuously rising anti-HBsAg serum Ab le vels with alternative isotype profiles (reflecting T1 or T2 polarization) i n transplanted HBs-tg hosts required donor CD4(+) T cell-dependent restimul ation of adoptively transferred immune cells by transgene-derived HBsAg, In jections of HBsAg-specific Abs into HBsAg mice did not establish stable hum oral immunity. The expanding T1 or T2 immune responses to HBsAg in HBs-tg h osts did not suppress transgene-directed HBsAg expression in the liver and did not induce liver injury. In addition to priming functional antiviral ef fector cells, the conditioning of the liver microenvironment to enable deli very of antiviral effector functions to this organ are therefore critical f or effective antiviral defense. A major challenge in the development of a t herapeutic vaccine against chronic hepatitis B or C virus infection is thus the efficient targeting of specifically induced immune effector specificit ies to the liver. The Journal of Immunology, 2000, 164: 4235-4243.