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Direct, help‐independent priming of CD8+ T cells by adeno‐associated virus–transduced hepatocytes
Author(s) -
Wuensch Sherry A.,
Spahn Jessica,
Crispe Ian N.
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23745
Subject(s) - cytotoxic t cell , priming (agriculture) , cd8 , t cell , biology , interleukin 21 , immunology , antigen , microbiology and biotechnology , immune system , in vitro , biochemistry , botany , germination
Both hepatitis B and C viruses frequently establish chronic infection, raising the question whether T cells are poorly primed in the liver. To determine the role of different cell types in the activation of CD8+ T cells against hepatocellular antigens, we used an Adeno‐associated virus to deliver ovalbumin to hepatocytes. In contrast to CD8+ T cells, CD4+ T cells were not activated. The CD8+ T cells were activated even in the absence of endogenous CD4+ T cells; however, in the liver, these cells were high in the programmed death‐1 protein and low in CD127. Chimera experiments revealed that these CD8+ T cells were activated on a solid tissue cell. Conclusion: Priming of CD8+ T cells directly on nonhematopoietic cells, in the absence of CD4+ T cell help, results in suboptimal T cell activation. This could explain the impaired function of CD8+ T cells seen in chronic liver infection. (H EPATOLOGY 2010)