gamma delta T cells are needed for ocular immune privilege and corneal graft survival

It has been recognized for over a century that the anterior chamber of the eye is endowed with a remarkable immune privilege. One contributing compone nt is the Ag-specific down-regulation of systemic delayed-type hypersensiti vity (DTH) that is induced when Ags are introduced into the anterior chambe r. This phenomenon, termed anterior chamber-associated immune deviation (AC AID), culminates in the generation of regulatory cells that inhibit the ind uction (afferent suppression) and expression (efferent suppression) of DTH. Since gamma delta T cells play a major role in other forms of immune regul ation, we suspected they might contribute to the induction and expression o f ACAID. Mice treated with anti-gamma delta Ab failed to develop ACAID foll owing anterior chamber injection of either soluble Ag (OVA) or alloantigens (spleen cells). Additional experiments with knockout mice confirmed that m ice lacking functional gamma delta T cells also fail to develop ACAID. Usin g a local adoptive transfer of DTH assay, we found that gamma delta T cells were required for the generation of regulatory T cells, but did not functi on as the efferent regulatory cells of ACAID. The importance of gamma delta T cells in corneal allograft survival was confirmed by blocking gamma delt a T cells with GL3 Ab before corneal transplantation. While in vivo treatme nt with normal hamster serum had no effect on corneal graft survival, infus ion of anti-gamma delta Ab resulted in a profound increase in corneal allog raft rejection. Thus, gamma delta T cells are needed for sustaining at leas t one aspect of ocular immune privilege and for promoting corneal allograft survival.