Purpose: Immune privilege in the eye is, in part, associated with the development of an antigen-specific systemic tolerance termed anterior chamber-associated immune deviation (ACAID). Natural killer T (NKT) cells express T-cell receptor and natural killer (NK) markers and are classified as innate immune cells partly because they produce cytokines within minutes of signals. The aim of this study was to elucidate the role of murine NKT cells in the induction of T regulatory cells in anterior chamber-associated immune deviation.
Methods: Anterior chamber-associated immune deviation T regulatory cell generation ability was examined in the following NKT cell-deficient mice: SJL mice, CDld or Jalpha281 knockout (KO) mice on C57BL/6 (B6) background, and NKT cell-depleted mice. To detect T regulatory cells, splenic T cells were harvested 7 days after anterior chamber inoculation of ovalbumin (50 microg/2 microL in Hanks balanced salt solution [HBSS]), mixed with ovalbumin-primed T cells (effector) and ovalbumin-pulsed antigen-presenting cells (stimulator), and then cotransferred into the ear pinnae of a syngeneic naive mouse (local adoptive transfer assay). Ear swelling was measured 24 hours later.
Results: Anterior chamber-inoculated B6 mice developed T regulatory cells, but all natural killer T cell-deficient mice did not generate T regulatory cells unless they were reconstituted with natural killer T cells. We also found that the number of splenic natural killer T cells were increased in anterior chamber-inoculated B6 mice and those natural killer T cells produced IL-10.
Conclusions: CD1d-reactive natural killer T cells are essential for the induction of T regulatory cells in anterior chamber-associated immune deviation through their IL-10 production and are involved in the maintenance of immune privilege of the eye.