Direct, help-independent priming of CD8+ T cells by adeno-associated virus-transduced hepatocytes.
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.


CONCLUSIONS
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.
Wuensch
Sherry A
SA
The David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Spahn
Jessica
J
Crispe
Ian N
IN
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000473:pathology; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D003713:Dendritic Cells / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology* / Q000821:virology*; D008099:Liver / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D061026:Programmed Cell Death 1 Receptor
D000943:Antigens, Differentiation; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor