Jinghua Wang, Brian Manick, Mark Renelt, Louis Hansen, Guoping Wu, and Vassilios Kalabokis
Cell surface-localized and secreted immunoglobulin superfamily (IgSF) proteins play central roles in regulating adaptive and innate immune responses, and are the primary targets for the development of new immunotherapeutics. In this work, we provide biologic and functional insight on VSIG8, one member of this important class of proteins. VSIG8 inhibits the production of cytokines (IL-2, IFN-gamma, IL-17, IL-6, and IL-19), chemokines (MCP-1, MCP-3, and IP-10), and other proteins (IGFBP-3 and RBP4) on anti-CD3 activated human CD3+ T cells. Furthermore, VSIG8 significantly reduces the production of IFN-gamma and IL-2 from both CD4+ and CD8+ T cells in the presence of T cell receptor signaling. In addition, VSIG8 markedly suppresses anti-CD3-induced human T cell proliferation and profoundly decreases the differentiation of naïve CD4+ T cells into Th1 cells. Thus, we have identified VSIG8 as a new immune checkpoint molecule that is able to inhibit human T cell activation. This novel human T cell co-inhibitory ligand may be a unique target for developing new immunotherapy strategies for the treatment of human cancers, autoimmune disorders, and infectious diseases.