γδ T cells are critical for the induction of anterior chamber-associated immune deviation

Anterior chamber-associated immune deviation (ACAID) is a systemic form of tolerance that is elicited by introducing antigens into the anterior chamber of the eye. ACAID is characterized by deficiencies in delayed-type hypersensitivity and complement-fixing antibodies upon subsequent challenge with antigen. The mechanisms responsible for the generation of this form of tolerance are not yet completely clear. Here we asked whether gamma delta T cells, which are critical in the induction of oral tolerance and nasal tolerance, play a role in ACAID. The percentage of splenic gamma delta T cells was higher in mice that received antigen via the anterior chamber compared to untreated mice. In addition, CD44 was up-regulated on some splenic gamma delta and alpha beta T cells after the intraocular injection of antigen. Moreover, administration of antigen into the anterior chamber did not induce ACAID in the C57BL/6 mice pretreated with anti-mouse delta -chain monoclonal antibody or in the gamma delta T-cell-receptor-deficient (delta (-/-)) mice. gamma delta T cells from wild-type mice reconstituted ACAID when transferred into the delta (-/-) mice before injection of antigen, verifying that the deficiency in delta (-/-) mice results from the lack of gamma delta T cells rather than from an inadvertent change caused by deletion of the delta -chain. These findings indicate that gamma delta T cells play a very important role in ocular tolerance.