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Local Intrahepatic CD8⁺ T Cell Activation by a Non-Self- Antigen Results in Full Functional Differentiation¹

Sherry A. Wuensch^2,*, Robert H. Pierce and I. Nicholas Crispe^*

^* David H. Smith Center for Vaccine Biology and Immunology, The Aab Institute for Biomedical Research, Departments of Microbiology and Immunology, and Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642

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- 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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