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Systemic antigen cross‐presented by liver sinusoidal endothelial cells induces liver‐specific CD8 T‐cell retention and tolerization
Author(s) -
von Oppen Nanette,
Schurich Anna,
Hegenbarth Silke,
Stabenow Dirk,
Tolba Rene,
Weiskirchen Ralf,
Geerts Albert,
Kolanus Waldemar,
Knolle Percy,
Diehl Linda
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22795
Subject(s) - cytotoxic t cell , antigen , antigen presentation , t cell , cd8 , biology , antigen presenting cell , cross presentation , major histocompatibility complex , immunology , microbiology and biotechnology , immune system , in vitro , biochemistry
Peripheral CD8 T‐cell tolerance can be generated outside lymphatic tissue in the liver, but the course of events leading to tolerogenic interaction of hepatic cell populations with circulating T‐cells remain largely undefined. Here we demonstrate that preferential uptake of systemically circulating antigen by murine liver sinusoidal endothelial cells (LSECs), and not by other antigen‐presenting cells in the liver or spleen, leads to cross‐presentation on major histocompatibility complex (MHC) I molecules, which causes rapid antigen‐specific naïve CD8 T‐cell retention in the liver but not in other organs. Using bone‐marrow chimeras and a novel transgenic mouse model (Tie2‐H‐2K b mice) with endothelial cell‐specific MHC I expression, we provide evidence that cross‐presentation by organ‐resident and radiation‐resistant LSECs in vivo was both essential and sufficient to cause antigen‐specific retention of naïve CD8 T‐cells under noninflammatory conditions. This was followed by sustained CD8 T‐cell proliferation and expansion in vivo , but ultimately led to the development of T‐cell tolerance. Conclusion: Our results show that cross‐presentation of circulating antigens by LSECs caused antigen‐specific retention of naïve CD8 T‐cells and identify antigen‐specific T‐cell adhesion as the first step in the induction of T‐cell tolerance. (H EPATOLOGY 2009.)