Antigen presentation by liver cells controls intrahepatic T cell trapping, whereas bone marrow-derived cells preferentially promote intrahepatic T cell apoptosis.
Systemic activation and proliferation of CD8(+) T cells result in T cell accumulation in the liver, associated with T cell apoptosis and liver injury. However, the role of Ag and APC in such accumulation is not clear. Bone marrow chimeras were constructed to allow Ag presentation in all tissues or alternatively to restrict presentation to either bone marrow-derived or non-bone marrow-derived cells. OVA-specific CD8(+) T cells were introduced by adoptive transfer and then activated using peptide, which resulted in clonal expansion followed by deletion. Ag presentation by liver non-bone marrow-derived cells was responsible for most of the accumulation of activated CD8(+) T cells. In contrast, Ag presentation by bone marrow-derived cells resulted in less accumulation of T cells in the liver, but a higher frequency of apoptotic cells within the intrahepatic T cell population. In unmodified TCR-transgenic mice, Ag-induced T cell deletion and intrahepatic accumulation of CD8(+) T cells result in hepatocyte damage, with the release of aminotransaminases. Our experiments show that such liver injury may occur in the absence of Ag presentation by the hepatocytes themselves, arguing for an indirect mechanism of liver damage.
Mehal
W Z
WZ
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Azzaroli
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F
Crispe
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IN
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D008099:Liver / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000276:immunology