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Priming of CD4 + T cells by liver sinusoidal endothelial cells induces CD25 low forkhead box protein 3 − regulatory T cells suppressing autoimmune hepatitis
Author(s) -
Kruse Nils,
Neumann Katrin,
Schrage Arnhild,
Derkow Katja,
Schott Eckart,
Erben Ulrike,
Kühl Anja,
Loddenkemper Christoph,
Zeitz Martin,
Hamann Alf,
Klugewitz Katja
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.23191
Subject(s) - immunology , foxp3 , biology , immune system , priming (agriculture) , cd40 , antigen , antigen presenting cell , antigen presentation , autoimmune hepatitis , t cell , proinflammatory cytokine , immune tolerance , inflammation , cytotoxic t cell , microbiology and biotechnology , hepatitis , in vitro , biochemistry , botany , germination
Elucidating cellular mechanisms that maintain the intrahepatic immune balance is crucial to our understanding of viral or autoimmune liver diseases and allograft acceptance. Liver sinusoidal endothelial cells (LSECs) play an important role in modifying local immune responses to tolerance in major histocompatibility complex (MHC) I–restricted models, whereas their contribution in the MHCII context is still controversial. In an MHCII chimeric mouse model that excludes MHCII‐mediated antigen presentation by professional antigen‐presenting cells, we demonstrated that LSECs prime CD4 + T cells to a CD45RB low memory phenotype lacking marker cytokine production for effector cells that was stable in vivo following immunogenic antigen re‐encounter. Although these cells, which we term T LSEC , had the capacity to enter lymph nodes and the liver, they did not function as effector cells either in a delayed‐type hypersensitivity reaction or in a hepatitis model. T LSEC inhibited the proliferation of naïve CD4 + T cells in vitro although being CD25 low and lacking expression of forkhead box protein (FoxP)3. Furthermore, these cells suppressed hepatic inflammation as monitored by alanine aminotransferase levels and cellular infiltrates in a T cell‐mediated autoimmune hepatitis model in vivo . Conclusion: T LSEC first described here might belong to the expanding group of FoxP3 − regulatory T cells. Our findings strengthen the previously discussed assumption that CD4 + T cell priming by nonprofessional antigen‐presenting cells induces anti‐inflammatory rather than proinflammatory phenotypes. Because recruitment of CD4 + T cells is increased upon hepatic inflammation, T LSEC might contribute to shifting antigen‐dependent immune responses to tolerance toward exogenous antigens or toward endogenous self‐antigens, especially under inflammatory conditions. (H EPATOLOGY 2009.)