Immune role of hepatic TLR-4 revealed by orthotopic mouse liver transplantation.
Activated CD8+ T cells migrate to the liver at the end of an immune response and go through apoptosis there, but this mechanism is impaired in mice lacking Toll-like receptor-4. This allowed us to test the importance of liver trapping in an ongoing immune response. In the absence of Toll-like receptor-4, reduced liver accumulation was associated with an increase in the circulating CD8+ T cell pool, more long-lived memory T cells and increased CD8+ T cell memory responses. Using experimental orthotopic liver transplantation, we showed that the effect of Toll-like receptor-4 on the formation of the CD8+ T cell memory resides in the liver.


CONCLUSIONS
These studies reveal a new function for the liver, which is to regulate the magnitude of T cell memory responses through a Toll-like receptor-4-dependent mechanism.
John
Beena
B
The David H Smith Center for Vaccine Biology and Immunology, The Aab Institute for Biomedical Research, University of Rochester, Rochester, NY 14642, USA. beena_john@urmc.rochester.edu
Klein
Ingo
I
Crispe
I Nicholas
IN
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002465:Cell Movement / Q000502:physiology; D005786:Gene Expression Regulation; D007156:Immunologic Memory / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000502:physiology; D016031:Liver Transplantation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4