Complete differentiation of CD8+ T cells activated locally within the transplanted liver.
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.
Klein
Ingo
I
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester, Rochester, NY 14642, USA. Klein_l@chirurgie.uni-wuerzburg.de
Crispe
Ian Nicholas
IN
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D007371:Interferon-gamma / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011828:Radiation Chimera / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology
D007371:Interferon-gamma