Gammadelta T cells in anterior chamber-induced tolerance in CD8(+) CTL responses

Delivery of antigen to the anterior chamber (AC) of the eye induces a systemic form of tolerance, referred to as anterior chamber-associated immune deviation (ACAID). ACAID is characterized by decreases in delayed-type hypersensitivity responses and complement-fixing antibodies on subsequent challenge with an immunogenic form of the antigen. The current study was designed to test whether priming of antigen-specific CD8(+) cytotoxic T-lymphocytes (CTLs) are inhibited by injection of soluble antigen into the AC and whether gammadelta T cells play a role in the inhibition of such responses.

Antigen was administered through the AC to normal gammadelta T-cell-deficient or reconstituted gammadelta T-cell-deficient mice. Seven days after the AC injection, the mice were primed with antigen in adjuvant and 10 days later, their spleen cells were cultured for 5 to 7 days and the CTL responses measured.

CTL responses were inhibited by antigen delivered through the AC in normal but not gammadelta T-cell-deficient mice. Tolerance was reconstituted in delta-chain knockout mice by the adoptive transfer of gammadelta T cells from normal mice. Moreover, spleen cells and splenic gammadelta(+) T cells, but not gammadelta(-) T cells, from mice injected with antigen through the AC inhibited development of CTL responses when cultured together with primed effector T cells.

These data show, for the first time, that administration of soluble antigen in the AC inhibits development of CD8(+) cytotoxic T-cell responses and that gammadelta T cells play a critical role in inhibition of CTL responses.