The role of hepatic immune regulation in systemic immunity to viral infection

被引:20
作者
Knolle, Percy A. [1 ]
Boettcher, Jan [2 ]
Huang, Li-Rung [3 ]
机构
[1] Tech Univ Munich, Inst Mol Immunol, Klinikum Rechts Isar, D-81675 Munich, Germany
[2] Canc Res UK, Immunobiol Lab, London Res Inst, London, England
[3] Natl Hlth Res Inst, Inst Mol & Genom Med, Miaoli, Taiwan
关键词
Liver immune regulation; Local antigen presentation; Liver-primed T cells; Liver sinusoidal endothelial cells; iMATE; Local T cell proliferation; Therapeutic vaccination; CD8(+) T-CELLS; LIVER ENDOTHELIAL-CELLS; DENDRITIC CELLS; CROSS-PRESENTATION; TOLERANCE; ANTIGEN; ACTIVATION; VIRUS; HEPATOCYTES; RECOGNITION;
D O I
10.1007/s00430-014-0371-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The liver has particular immune functions attributed by its unique microenvironment and its liver-resident cell populations. During autoimmunity and viral hepatitis, the liver serves as target for effector responses of immune cells. However, skewing of effector T cell functions through tolerogenic liver-resident antigen-presenting cells and through the immune regulatory hepatic microenvironment. Importantly, the liver also participates in shaping systemic antigen-specific immunity. Local antigen-presenting cell populations, in particular liver sinusoidal endothelial cells (LSECs), cross-present soluble, circulating or hepatocyte-derived antigens to na < ve CD8 T cells. Upon priming by cross-presenting LSECs, na < ve CD8 T cells develop into a unique population of antigen-experienced memory-like T cell population that can be reactivated in an inflammatory context to protect against infection with viruses or bacteria. Furthermore, upon prolonged inflammatory TNF-dependent signaling, the induction of intrahepatic myeloid cell aggregates for T cell population expansion (iMATEs) is observed in liver tissue. iMATEs are formed by inflammatory monocytes developing into dendritic cells and function to attract recently activated CD8 T cells. Those CD8 T cells located within the cocoon-like iMATE structure show strong proliferation initiated by co-stimulatory signaling. Locally expanded CD8 T cells are key to control acute and chronic viral infections. The mechanistic understanding of local hepatic T cell priming and local expansion of effector CD8 T cells will help to develop novel therapeutic vaccination strategies.
引用
收藏
页码:21 / 27
页数:7
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