Local intrahepatic CD8+ T cell activation by a non-self-antigen results in full functional differentiation.
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.
Wuensch
Sherry A
SA
David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. sherry_wuensch@URMC.rochester.edu
Pierce
Robert H
RH
Crispe
I Nicholas
IN
D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D000229:Dependovirus / Q000276:immunology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000276:immunology*; D022781:Hepatocytes / Q000166:cytology* / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015415:Biomarkers; D018960:Hyaluronan Receptors; C485184:enhanced green fluorescent protein; D019041:L-Selectin; D049452:Green Fluorescent Proteins; D010047:Ovalbumin