H-2(d) mice born to and reared by HBeAg-transgenic mothers do not develop T cell tolerance toward the hepatitis B virus core gene products

The function of the secretory core gene product (HBeAg) of the human hepati tis B virus (HBV) is unknown. It has been proposed that this protein may be passed from the mother to her offspring at the perinatal stage where it mi ght induce immune tolerance. In a previous study we have shown that the mur ine placenta presents an efficient barrier for the HBe protein and that H-2 (b) mice born to HBeAg-positive transgenic mothers do not develop tolerance of specific cytotoxic T cells. In the present work we demonstrate that tra nsgenic mice expressing high serum levels of HBeAg secrete only small amoun ts of this protein into their milk and excrete minute amounts of the viral gene product in their urine. Furthermore, it is shown that nontransgenic H- 2(d) mice born to and reared by HBeAg-positive mothers exhibit a reactivity of HBc/eAg-specific CD4(+) Th cells and CD8(+) cytotoxic T cells comparabl e to that of normal isogenic control mice. In accordance with this observat ion the humoral immune responses directed against the HBeAg were comparable between these two groups of animals. This finding indicates that H-2(d) mi ce potentially exposed to small amounts of maternal HBeAg transferred by th e transplacental, lactogenic, or renal route do not develop tolerance towar d the HBV core gene products. These data challenge the hypothesis that a po tential function of the HBeAg may be to operate as a tolerogen at the perin atal developmental stage. (C) 2000 Academic Press.