Abstract: |
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. Copyright © 2005 by the American Association for the Study of Liver Diseases. |
Keywords: |
controlled study; nonhuman; cd3 antigen; lymphocyte proliferation; t lymphocyte; animal cell; mouse; animals; mice; interleukin 2; spleen; interleukin 10; interleukin 4; interleukin 5; mice, inbred balb c; mice, inbred c57bl; liver; lymphocyte activation; cytokines; dendritic cells; immune tolerance; gamma interferon; cd4-positive t-lymphocytes; natural killer cell; cytokine production; cell stimulation; environmental factor; fluorescence activated cell sorting; lymphocyte function; interleukin-2; spleen cell; receptors, antigen, t-cell, gamma-delta; cd4-cd8 ratio
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