MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses

Immunity. 1994 Aug;1(5):433-42. doi: 10.1016/1074-7613(94)90074-4.


The use of E1-deleted recombinant adenoviruses in gene therapy has consistently been associated with transient gene expression and inflammation due to immune-based destruction of the infected cells. We have used murine models of adenovirus-mediated gene transfer to liver to investigate these immunologic mechanisms. Adoptive transfer experiments, as well as studies involving genetic knockout mice, confirmed the original hypothesis that cell-mediated immunity induced by E1-deleted adenovirus destroyed trans-gene-expressing hepatocytes and defined MHC class I-restricted CD8+ cytolytic lymphocytes as the primary immune effectors for hepatocyte destruction. Responses mediated by CD4+ cells per se were insufficient to mediate destruction of hepatocytes in vivo, despite the activation of virus-specific T helper cells of Th1 subsets. A better understanding of the response of the host to in vivo gene therapy is important in evaluating its usefulness in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae Infections / immunology*
  • Adenovirus E1 Proteins / immunology*
  • Animals
  • Antigens, Viral / analysis
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes
  • Gene Transfer Techniques
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class II / immunology
  • Liver / cytology*
  • Liver / virology
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins / immunology
  • Spleen / cytology
  • T-Lymphocyte Subsets / virology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / virology


  • Adenovirus E1 Proteins
  • Antigens, Viral
  • Epitopes
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Recombinant Proteins