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 hepatitis 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 might induce immune tolerance. In a previous study we have shown that the murine 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 transgenic mice expressing high serum levels of HBeAg secrete only small amounts 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 comparable to that of normal isogenic control mice. In accordance with this observation the humoral immune responses directed against the HBeAg were comparable between these two groups of animals. This finding indicates that H-2(d) mice potentially exposed to small amounts of maternal HBeAg transferred by the transplacental, lactogenic, or renal route do not develop tolerance toward the HBV core gene products. These data challenge the hypothesis that a potential function of the HBeAg may be to operate as a tolerogen at the perinatal developmental stage.
Merkle
H
H
Department of Internal Medicine I, Laboratory Animal Research Unit, University of Ulm, Albert Einstein Allee 11, Ulm, 89081, Germany.
Deutschle
T
T
Gastrock-Balitsch
I
I
Nusser
P
P
Knehr
S
S
Reifenberg
K
K
D000818:Animals; D000831:Animals, Newborn; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000652:urine; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry / Q000821:virology; D009035:Mothers; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D006183:H-2 Antigens; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D010446:Peptide Fragments