The Journal of Experimental Medicine
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Published online 13 February 2006 doi:10.1084/jem.20051775
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 2, 437-447
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ARTICLE

 Complete differentiation of CD8+ T cells activated locally within the transplanted liver

Ingo Klein1,2 and Ian Nicholas Crispe1

1 David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester, Rochester, NY 14642
2 Department of Surgery, University of Würzburg, D-97080 Würzburg, Germany

CORRESPONDENCE Ingo Klein: Klein_I@chirurgie.uni-wuerzburg.de

The transplanted liver elicits systemic tolerance, and the underlying mechanism may also account for the persistence of liver infections, such as malaria and viral hepatitis. These phenomena have led to the hypothesis that antigen presentation within the liver is abortive, leading to T cell tolerance or apoptosis. Here we test this hypothesis in an optimized orthotopic liver transplantation model. In direct contradiction to this model, the liver itself induces full CD8+ T cell activation and differentiation. The effects of microchimerism were neutralized by bone marrow transplantation in the liver donor, and the lack of liver-derived antigen-presenting cells was documented by eight-color flow cytometry and by sensitive functional assays. We conclude that local antigen presentation cannot explain liver tolerance. On the contrary, the liver may be an excellent priming site for naive CD8+ T cells.

Abbreviations used: bm8, B6.C-H-2bm8 mouse strain; IVC, inferior vena cava; LSEC, liver sinusoidal endothelial cell.


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