Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells

JOURNAL OF HEPATOLOGY

卷:49

Article

Tokita, Daisuke^1,2  Sumpter, Tina L.^1,2  Ralmondi, Giorgio^1,2  Zahorchak, Alan F.^1,2  Wang, Zhiliang^1,2  Nakao, Atsunorl^1,2  Mazariegos, George V.^1,2  Abe, Masanorl^1,2  Thomson, Angus W.^1,2,3 

[1] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA

[3] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15213 USA

关键词: Dendritic cells;    Liver;    T cells;    Mouse;    Endotoxin;    Toll-like receptor;    Tolerance;   

DOI  :  10.1016/j.jhep.2008.07.028

来源: Elsevier

【 摘 要 】

Background/Aims:The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC), - innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Methods: Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-treated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally occurring regulatory T cells (Treg). Results: While IL-10 production was greater for freshly isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4(+)T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4(+)CD25(+) regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. Conclusions: The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free