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Published on: September 12, 2019
A microsurgical approach to hepatic and extrahepatic antigen presentation and its effects on the migration pattern of
Ingo Klein1, Heinz-Jochen Gassel, Arnulf Thiede
1David H. Smith Center for Vaccine Biology and Immunology/Aab Institute of Biomedical Sciences, University of Rochester School of Medicine, Rochester, NY, USA. klein_l@chirurgie.uni-wuerzburg.de
CD8+T lymphocytes activated in peripheral lymphoid organs are believed to preferentially localize to the hepatic sinusoids, but the role of antigen in the process has been difficult to define. To create experimental mice in which the liver was unique in lacking the ability to present antigen, we adopted a novel microsurgical approach, in which the site of antigen presentation was restricted by orthotopic mouse liver transplantation of MHC Class I-disparate livers. We used two related mouse strains, of which the wild-type strain could present an injectable model antigen, while a mutant strain could not. By transplanting mutant-strain livers into wild type recipients, we were able to evaluate the absence of intrahepatic parenchymal antigen presentation on CD8+ T cell activation, differentiation, and migration. This illustrates that orthotopic liver transplantation is a powerful technique for addressing issues of antigen presentation.
CD8+T lymphocytes activated in peripheral lymphoid organs are believed to preferentially localize to the hepatic sinusoids, but the role of antigen in the process has been difficult to define. To create experimental mice in which the liver was unique in lacking the ability to present antigen, we adopted a novel microsurgical approach, in which the site of antigen presentation was restricted by orthotopic mouse liver transplantation of MHC Class I-disparate livers. We used two related mouse strains, of which the wild-type strain could present an injectable model antigen, while a mutant strain could not. By transplanting mutant-strain livers into wild type recipients, we were able to evaluate the absence of intrahepatic parenchymal antigen presentation on CD8+ T cell activation, differentiation, and migration. This illustrates that orthotopic liver transplantation is a powerful technique for addressing issues of antigen presentation.
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