Deciphering the Role of VSIG-3 as a VISTA Ligand in Human T-Cell Regulation

The B7 family and their receptors are integral in modulating T-cell responses, offering potential targets for immunotherapy. This study uncovers a new interaction between VSIG-3/IGSF11 and the B7 family member VISTA/PD-1H, which suppresses human T-cell functions through a novel pathway. An extensive ELISA binding screening assay identified a specific binding between VSIG-3 and VISTA, with no observed interaction with other B7 family members under the same conditions. Notably, VSIG-8 was found to have no significant interaction with VISTA.

VSIG-3 has been shown to inhibit T-cell proliferation even in the presence of T-cell receptor signaling and to markedly reduce the production of various cytokines and chemokines by human T cells. Anti-VISTA neutralization antibodies were found to mitigate the binding between VSIG-3 and VISTA, as well as the T-cell inhibition induced by VSIG-3.

The identification of VSIG-3 as a ligand for VISTA that can suppress human T-cell proliferation and cytokine production presents a new co-inhibitory pathway. This discovery could pave the way for new therapeutic strategies for a range of conditions, including cancer, autoimmune diseases, infections, and transplant rejection, and may also contribute to the development of more effective vaccines.