A microsurgical approach to hepatic and extrahepatic antigen presentation and its effects on the migration pattern of activated CD8(+) T cells.
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.
Klein
Ingo
I
David 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
Gassel
Heinz-Jochen
HJ
Thiede
Arnulf
A
Crispe
Ian Nicholas
IN
Steger
Ulrich
U
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I