Monoclonal antibody against human Tim‐3 enhances antiviral immune response. (4th January 2019)

• Record Type: Journal Article
• Authors: Li, Ge; Hou, Chunmei; Dou, Shuaijie; Zhang, Jiacheng; Zhang, Yanling; Liu, Yiqiong; Wang, Zhiding; Xiao, He; Wang, Renxi; Chen, Guojiang; Li, Yan; Feng, Jiannan; Shen, Beifen; Han, Gencheng
• Is Part Of: Scandinavian journal of immunology. Volume 89:Number 2(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-01-04
• Subjects: H1N1 -- immune tolerance -- monoclonal antibody -- Tim‐3; Immunology -- Periodicals; 571.96
• DOI: 10.1111/sji.12738
• Languages: English
• ISSNs: 0300-9475

Abstract

Abstract: T cell immunoglobulin and mucin domain protein 3 (Tim‐3) is an immune checkpoint inhibitor in T cells and innate immune cells. The deregulated upregulation of Tim‐3 is related to immune exhaustion in tumour and viral infection. To overcome Tim‐3‐mediated immune tolerance, we developed a novel monoclonal antibody against human Tim‐3 (L3G) and investigated its roles in inhibiting Tim‐3 signalling and overcoming immune tolerance in T cells and monocytes/macrophages. The administration of L3G to cultured peripheral blood mononuclear cells (PBMCs) significantly increased the production of IFN‐γ and IL‐2 and the expression of type I interferon. The administration of L3G also increased the production of IFN‐γ, IL‐8 and type I interferon in U937 cells and primary monocytes. We investigated the mechanisms by which L3G enhances pro‐inflammatory cytokine expression, and our data show that L3G enhances STAT1 phosphorylation in both monocytes/macrophages and T cells. Finally, in an H1N1 infection model of PBMCs and U937 cells, L3G decreased the viral load and enhanced the expression of interferon. Thus, we developed a functional antibody with therapeutic potential against Tim‐3‐mediated infection tolerance.