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Differential dynamics of the peripheral and intrahepatic cytotoxic T lymphocyte response to hepatitis B surface antigen |
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| Authors: | Isogawa Masanori Kakimi Kazuhiro Kamamoto Hiroyuki Protzer Ulrike Chisari Francis V |
| Affiliation: | a Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA b Fourth Department of Internal Medicine, Tokyo Medical University, Tokyo 160-0023, Japan c Molecular Infectiology, Center for Molecular Medicine, Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, D-50935 Koln, Germany |
| Abstract: | The distribution and dynamics of the cytotoxic T lymphocyte (CTL) response to hepatitis B surface antigen (HBsAg) were studied in mice after intramuscular DNA immunization and after hepatic infection by a recombinant adenovirus that expresses the hepatitis B virus genome (Ad-HBV). CTLs specific for HBsAg accumulate preferentially in the spleen after DNA immunization but are primarily intrahepatic after Ad-HBV infection. The secondary CTL response to Ad-HBV in DNA-primed mice is characterized by rapid depletion of effector CTLs from the spleen, and their expansion in the liver where they cause hepatitis, secrete interferon gamma (IFNγ), and inhibit HBV gene expression. Suppression of HBsAg synthesis is accompanied by disappearance of intrahepatic IFNγ-producing CTLs and their reaccumulation in the spleen. The data suggest a possible explanation for the paucity and functional deficiency of HBV-specific CTLs in the periphery during chronic HBV infection, and that the severity of infection can be worsened by a preexisting CTL response if neutralizing antibody is not also present. |
| Keywords: | Hepatitis B virus Cytotoxic T lymphocytes Interferon gamma Adenovirus Anergy |
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