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J Immunol. 2006 Aug 1;177(3):1689-97.

Local intrahepatic CD8+ T cell activation by a non-self-antigen results in full functional differentiation.

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  • 1David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.


The response of T cells to liver Ags sometimes results in immune tolerance. This has been proposed to result from local, intrahepatic priming, while the expression of the same Ag in liver-draining lymph nodes is believed to result in effective immunity. We tested this model, using an exogenous model Ag expressed only in hepatocytes, due to infection with an adeno-associated virus vector. T cell activation was exclusively intrahepatic, yet in contrast to the predictions of the current model, this resulted in clonal expansion, IFN-gamma synthesis, and cytotoxic effector function. Local activation of naive CD8(+) T cells can therefore cause full CD8(+) T cell activation, and hepatocellular presentation cannot be used to explain the failure of CTL effector function against some liver pathogens such as hepatitis C.

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