Oncotarget

Research Papers: Immunology:

Hepatic stroma-educated regulatory DCs suppress CD8+ T cell proliferation in mice

Qian Wang, Hao He, Dongwei Chen, Chao Wang, Yingping Xu and Wengang Song _

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Oncotarget. 2017; 8:93414-93425. https://doi.org/10.18632/oncotarget.18459

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Abstract

Qian Wang1,2,*, Hao He1,*, Dongwei Chen3, Chao Wang3, Yingping Xu1 and Wengang Song1

1 Institute of Immunology, Taishan Medical University, Taian, Shandong, China

2 Center Hospital of Taian City, Taian, Shandong, China

3 Institute of Immunology, School of Medicine, Tsinghua University, Beijing, China

* These authors have contributed equally to this work

Correspondence to:

Wengang Song, email:

Keywords: liver, regulatory dendritic cells, CD8+ T cells, nitric oxide, autoimmune hepatitis, Immunology and Microbiology Section, Immune response, Immunity

Received: February 03, 2017 Accepted: May 22, 2017 Published: June 13, 2017

Abstract

Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the CD4+ T cell response. The present study assessed whether and how liver DCs suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells to express CD25 and CD69, but inhibited their proliferation. CD8+ T cell suppression depended on soluble factors released by LSed-DCs, but not cell-cell contact. Compared with mature DCs, LSed-DCs produced more nitric oxide and IL-10. Addition of a nitric oxide synthase inhibitor, PBIT, but not an IL-10-blocking mAb, reversed LSed-DC inhibition of CD8+ T cell proliferation. We also found that LSed-DCs reduced CD8+ T cell-mediated liver damage in a mouse model of autoimmune hepatitis. These results demonstrate that the liver stroma induces mature DCs to differentiate into regulatory DCs that suppress CD8+ T cell proliferation, and thus contribute to liver tolerance.


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