Immune role of hepatic TLR-4 revealed by orthotopic mouse liver transplantation

Authors

  • Beena John,

    Corresponding author
    1. The David H. Smith Center for Vaccine Biology and Immunology, The Aab Institute for Biomedical Research, University of Rochester, Rochester, NY
    • David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 609, Rochester, NY 14642, USA
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    • fax: 585-273-2452

  • Ingo Klein,

    1. The David H. Smith Center for Vaccine Biology and Immunology, The Aab Institute for Biomedical Research, University of Rochester, Rochester, NY
    2. Department of Surgery, University Hospital Wuerzburg, Julius-Maximilians University, Wuerzburg, Germany
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  • I. Nicholas Crispe

    1. The David H. Smith Center for Vaccine Biology and Immunology, The Aab Institute for Biomedical Research, University of Rochester, Rochester, NY
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  • Potential conflict of interest: Nothing to report.

Abstract

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. Conclusion: 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. (HEPATOLOGY 2007;45:178–186.)

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