Effect of intraocular gamma-interferon on immunoregulatory properties of iris and ciliary body cells.

Resistance of the anterior chamber (AC) of mouse eyes to expression of cell-mediated immunity can be overcome by pre-treating the eye with a dose of recombinant rat gamma-interferon (gamma IFN) that is of itself noninflammatory. To study the mechanism of this form of intraocular inflammation, cells of the tissues surrounding the AC (iris, ciliary body, cornea) were studied in vivo for alterations in phenotype and in vitro regarding their effects on antigen-driven T cell activation. The results indicate that gamma IFN: (1) induced class II major histocompatibility complex (MHC) expression on resident bone marrow-derived cells of iris and ciliary body (I/CB), but not the cornea; (2) led to recruitment of bone marrow-derived cells into the I/CB stroma; and (3) failed to induce class II MHC expression on ocular epithelial cells. Cell suspensions prepared from gamma IFN-treated I/CB superficially resembled normal I/CB cells in that neither were able to activate allogeneic T cells and both were able to suppress antigen-driven T cell activation in vitro. However, unlike cells from normal eyes, I/CB cells from gamma IFN-treated eyes suppressed T cell activation primarily through the secretion of prostaglandins. These results indicate that the ability of gamma IFN-treated eyes to display immunogenic inflammation probably does not result merely from the restoration of conventional antigen presenting cells to this environment, but appears to correlate with a critical change in the molecular mediators of immunosuppression. The findings are discussed in terms of the possibility that the eye may be able to respond to abrogation of its primary immunosuppressive microenvironment by erecting a secondary microenvironment that also is capable of suppressing immunogenic inflammation with a different set of antiinflammatory mediators.