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Tomoyuki Kunishige, Hiroko Taniguchi, Tatsukuni Ohno, Miyuki Azuma, Junko Hori; Mechanisms of V-domain Ig suppressor of T cell activation (VISTA)-mediated acceptance of corneal allografts. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4872.
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© ARVO (1962-2015); The Authors (2016-present)
V-domain Ig suppressor of T cell activation (VISTA) is a novel and structurally distinct Ig superfamily inhibitory ligand. We have previously demonstrated that survival of allografts treated with anti-VISTA mAb was less than that of the control, and that VISTA plays important role in induction of alloantigen-specific ACAID. (1) To further investigate the mechanism of VISTA-mediated corneal allograft survival, we examined destruction of corneal endothelial cells (CECs) by allo-reactive T cells in vitro. (2) As the next, we examined infiltrating T cells in the graft-bearing eyes from the recipients treated with anti-VISTA or control IgG.
The corneas from C57BL/6 (B6) eyes pre-treated with anti-VISTA mAb or control rat IgG were incubated with CD4+ T cells for 6h. Dead CECs stained with propidium iodide were counted and compared. (2) Normal corneas of C57BL/6 were transplanted into normal eyes of BALB/c mice. Recipients were administrated with 0.2 mg of anti-VISTA mAb or control rat IgG, three times a week after grafting. For Immunohistochemical staining, graft-bearing eyes were removed.
No significant differences were observed between the number of dead CECs treated with anti-VISTA monoclonal antibodies (mAb) and that treated with control IgG after incubation with allo-reactive T cells. It is indicated that VISTA does not have protective effect in the cornea from the allo-specific killing by CD4 T cells. (2) Immunofluorescent staining of the graft-bearing eyes at 3 to 5 weeks after grafting revealed that the number of infiltrating CD4+ T cells and CD8+ T cells at graft center and host-graft junction were significantly higher in anti-VISTA treated recipients compared to control.
Taken together of our present and previous data, it is suggested that VISTA plays an role in the acceptance of corneal allografts by inducing allo-specific ACAID which suppress T cell infiltration into the cornea, although VISTA doesn’t have a local protective effect in the interaction between CECs and CD4+ T cells.
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