γδ T Cells Are Needed for Ocular Immune Privilege and Corneal Graft Survival

Abstract

It has been recognized for over a century that the anterior chamber of the eye is endowed with a remarkable immune privilege. One contributing component is the Ag-specific down-regulation of systemic delayed-type hypersensitivity (DTH) that is induced when Ags are introduced into the anterior chamber. This phenomenon, termed anterior chamber-associated immune deviation (ACAID), culminates in the generation of regulatory cells that inhibit the induction (afferent suppression) and expression (efferent suppression) of DTH. Since γδ T cells play a major role in other forms of immune regulation, we suspected they might contribute to the induction and expression of ACAID. Mice treated with anti-γδ Ab failed to develop ACAID following anterior chamber injection of either soluble Ag (OVA) or alloantigens (spleen cells). Additional experiments with knockout mice confirmed that mice lacking functional γδ T cells also fail to develop ACAID. Using a local adoptive transfer of DTH assay, we found that γδ T cells were required for the generation of regulatory T cells, but did not function as the efferent regulatory cells of ACAID. The importance of γδ T cells in corneal allograft survival was confirmed by blocking γδ T cells with GL3 Ab before corneal transplantation. While in vivo treatment with normal hamster serum had no effect on corneal graft survival, infusion of anti-γδ Ab resulted in a profound increase in corneal allograft rejection. Thus, γδ T cells are needed for sustaining at least one aspect of ocular immune privilege and for promoting corneal allograft survival.