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VSIG ‐3 as a ligand of VISTA inhibits human T‐cell function
Author(s) -
Wang Jinghua,
Wu Guoping,
Manick Brian,
Hernandez Vida,
Renelt Mark,
Erickson Christian,
Guan Joanna,
Singh Ravinder,
Rollins Simone,
Solorz Alicia,
Bi Ming,
Li Jun,
Grabowski David,
Dirkx Janette,
Tracy Camrin,
Stuart Thomas,
Ellinghuysen Chad,
Desmond Daniel,
Foster Craig,
Kalabokis Vassilios
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13001
Subject(s) - ccl5 , t cell , ccl3 , chemokine , cytokine , microbiology and biotechnology , cxcl11 , receptor , cell growth , biology , ligand (biochemistry) , chemistry , chemokine receptor , immunology , immune system , il 2 receptor , biochemistry , ccl2
Summary B7 family members and their receptors play a central role in the regulation of T‐cell responses through T‐cell co‐stimulation and co‐inhibition pathways that constitute attractive targets for the development of immunotherapeutic drugs. In this study, we report that VSIG ‐3/ IGSF 11 is a ligand of B7 family member VISTA / PD ‐1H and inhibits human T‐cell functions through a novel VSIG ‐3/ VISTA pathway. An extensive functional ELISA binding screening assay reveals that VSIG ‐3 binds to the new B7 family member VISTA but does not interact with other known members of the B7 family. Under the same experimental conditions, we did not observe any significant interaction between VSIG ‐8 and VISTA . In addition, VSIG ‐3 inhibits human T‐cell proliferation in the presence of T‐cell receptor signaling. Furthermore, VSIG ‐3 significantly reduces cytokine and chemokine production by human T cells including IFN ‐ γ , IL ‐2, IL ‐17, CCL 5/Rantes, CCL 3/ MIP ‐1 α , and CXCL 11/I‐ TAC . Anti‐ VISTA neutralization antibodies attenuate the binding of VSIG ‐3 and VISTA , as well as VSIG ‐3‐induced T‐cell inhibition. Hence, we have identified a novel ligand for VISTA that is able to inhibit human T‐cell proliferation and cytokine production. This unique VSIG ‐3/ VISTA co‐inhibitory pathway may provide new strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may aid in the design of better vaccines.