Influence of CD8 T cell priming in liver and gut on the enterohepatic circulation.

Autor: Eickmeier I; Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin, CVK, Berlin, Germany., Seidel D; Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin, CVK, Berlin, Germany., Grün JR; German Rheumatism Research Center, Berlin, Germany., Derkow K; Dept. of Neurology, Charité Universitätsmedizin, CCM, Berlin, Germany., Lehnardt S; Dept. of Neurology, Charité Universitätsmedizin, CCM, Berlin, Germany; Cluster of Excellence NeuroCure, Charité Universitätsmedizin Berlin, Germany., Kühl AA; Dept. of Gastroenterology, Infectious Diseases and Rheumatology, Charité Universitätsmedizin, CBF, Berlin, Germany., Hamann A; Dept. of Rheumatology and Clinical Immunology, Charité Universitätsmedizin, CCM, Berlin, Germany., Schott E; Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin, CVK, Berlin, Germany. Electronic address: eckart.schott@charite.de.
Jazyk: angličtina
Zdroj: Journal of hepatology [J Hepatol] 2014 Jun; Vol. 60 (6), pp. 1143-50. Date of Electronic Publication: 2014 Feb 19.
DOI: 10.1016/j.jhep.2014.02.011
Abstrakt: Background & Aims: The enterohepatic circuit of T cells may be responsible for the development of autoimmune liver disease. We employed transgenic mice to characterize phenotype and migration patterns of CD8 T cells activated in liver and gut.
Methods: We studied the migration of antigen-specific CD8 T cells primed in liver or gut after transfer in wild-type mice or mice that express ovalbumin in liver or gut. We performed transcriptome analysis of these two distinct T cell populations and confirmed our findings by flow cytometry.
Results: Specific migration patterns were induced by activation of CD8 T cells in gut or liver. Gut-activated CD8 T cells expressed α4β7 and CCR9 and migrated to the gut and to the liver. Liver-activated T cells expressed integrins α4, α6, β1, α4β7 as well as CD62L, Ly6C, and neuropilin-1 and retained the capability to re-circulate through lymph nodes. Presence of the antigen increased retention of both types of activated T cells in the liver, but migration of liver-activated T cells to the gut was prohibited.
Conclusions: CD8 T cells primed in the liver in vivo are not capable of migrating to the gut, implying that the enterohepatic circuit of CD8 T cells is in fact a one-way road from the gut to the liver. Priming of CD8 T cells in the liver results in a distinct phenotype with attributes of central memory cells and induces a unique homing pattern. Gut-primed T cells preferentially home to the liver, in principle enabling them to induce autoimmune liver disease.
(Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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