A microsurgical approach to hepatic and extrahepatic antigen presentation and its effects on the migration pattern of activated CD8(+) T cells.

Abstract

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.