VISTA Is Crucial for Corneal Allograft Survival and Maintenance of Immune Privilege

PURPOSE. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand for regulating T cell proliferation and cytokine production. The purpose of the present study was to determine the role of VISTA in the immune privilege of corneal allografts. METHODS. Expression of VISTA mRNA in mouse eyes was assessed with reverse-transcription PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c wildtype recipients treated with anti-VISTA mAb, and graft survival was assessed. A separate set of BALB/c mice treated with anti-VISTA mAb or rat IgG received injection of C57BL/6 splenocytes into the anterior chamber, and induction of allospecific anterior chamber-associated immune deviation (ACAID) was assessed. CD4(+) and CD8(+) T cells in the spleen were assessed with flow cytometry. RESULTS. VISTA mRNA was constitutively expressed in the cornea, and the expression of VISTA was localized to CD11b(+) cells on the corneal stroma. Survival of allografts treated with anti-VISTA mAb was less than that of the control. ACAID was induced less efficiently in BALB/c mice treated with VISTA mAb. The proportions of CD8(+) T cells and CD8(+) CD103(+) T cells (CD8(+) T regulatory cells) in the spleen of BALB/c mice treated with anti-VISTA mAb were significantly lower than those of the control. CONCLUSIONS. VISTA may play an essential role in the acceptance of corneal allografts via involvement with allospecific ACAID, which suppresses T cell infiltration into the cornea.