Abstract
Purpose:
A novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1, was identified. This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. The expression and function of VISTA in the eye remain largely unknown. The purpose of the present study was to determine the role of VISTA in immune privilege of corneal allografts.
Methods:
Normal corneas of C57BL/6 were transplanted orthotopically into normal eyes of BALB/c mice. Recipients were administrated intraperitoneally with 0.2 mg of anti-VISTA monoclonal antibodies (mAb) or control rat IgG, three times a week for 8 weeks after grafting. Graft survival was assessed clinically and was compared. Expression of VISTA in allografts was assessed immunohistochemically by confocal microscopy.
Results:
Survival of allografts treated with anti-VISTA mAb was less than that of the control. Control allografts were infiltrated by small number of CD4+cells which strongly expressed VISTA. On the other hands, blockade of VISTA by mAb led to infiltration of a lot of CD4+T cells which did not express VISTA, and resulted in allograft rejection.
Conclusions:
VISTA plays important role in acceptance of corneal allografts. It is suggested that VISTA contribute to Immune privilege of the corneal allografts.
Keywords: 553 immune tolerance/privilege •
555 immunomodulation/immunoregulation •
741 transplantation