Premium
Monoclonal antibody against human Tim‐3 enhances antiviral immune response
Author(s) -
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
Publication year - 2019
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12738
Subject(s) - immune system , immunology , biology , interferon , monoclonal antibody , cytokine , antibody , u937 cell , peripheral blood mononuclear cell , innate immune system , monocyte , il 2 receptor , peripheral tolerance , immune tolerance , t cell , virology , cell culture , biochemistry , genetics , in vitro
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.