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Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors
Author(s) -
Katz Steven C.,
Pillarisetty Venu G.,
Bleier Joshua I.,
Kingham T. Peter,
Chaudhry Umer I.,
Shah Alaap B.,
DeMatteo Ronald P.
Publication year - 2005
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.20795
Subject(s) - spleen , interleukin 21 , natural killer t cell , t cell , interleukin 12 , biology , cytotoxic t cell , antigen , immunology , microbiology and biotechnology , immune system , in vitro , biochemistry
The contribution of intrahepatic conventional T cells to the unique immunologic properties of the liver has not been clearly defined. We isolated bulk and CD4 T cells from mouse liver and compared their functions with each other and with their splenic counterparts. Unlike bulk spleen T cells, bulk liver T cells reacted minimally to allogeneic or antigen‐loaded syngeneic dendritic cells. However, after exclusion of natural killer T cells (NKTs) and γδ T cells by FACS, liver and spleen CD4 T cells actually proliferated to a similar extent upon allogeneic or antigen‐specific stimulation. Liver CD4 T cells were more sensitive to interleukin 2 (IL‐2) than were spleen CD4 T cells, but had a similar proliferative potential based on their response to CD3 ligation. In addition, activated liver CD4 T cells produced higher levels of IL‐4, IL‐5, IL‐10, and interferon gamma (IFN‐γ) than did splenic CD4 T cells. Therefore, liver CD4 T cells are intrinsically different from spleen CD4 T cells. In vitro, liver or spleen NKTs and γδ T cells suppressed liver and spleen CD4 T‐cell proliferation in a dose‐dependent fashion. In conclusion , unconventional T cells constrain liver CD4 T‐cell function. Our findings have implications for pathological conditions of the liver that involve the response of conventional CD4 T lymphocytes. (H EPATOLOGY 2005;42:293–300.)