Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors

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.)