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

// Qian Wang 1,2,* , Hao He 1,* , Dongwei Chen 3 , Chao Wang 3 , Yingping Xu 1 and Wengang Song 1 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.