Effects of experimental ocular inflammation on ocular immune privilege

PURPOSE. TO determine whether the inflammation of endotoxin-induced uveitis (EIU) andexperi mental autoimmune uveoretinitis (EAU) alters key in vivo a nd in vitro parameters of ocular immune privilege. METHODS. For EIU induction, C3H/HeN mice received 200 mu g lipopolysacchari de (LPS). Por EAU induction, B10.A mice were immunized with 50 mu g interph otoreceptor retinoid-binding protein (IRBP) mixed with complete Freund's ad juvant. aqueous humor (AqH) was collected at periodic intervals and assayed for leukocyte content and the ability to suppress or enhance T-cell prolif eration. Eyes with EAU were assessed for the capacity to support anterior c hamber (AC)-associated immune deviation (ACAID) induction after injection o f ovalbumin (OVA). RESULTS. Inflammation within the anterior segment in EIU peaked at 12 to 24 hours and was detected from 10 days onward in EAU. In AqH of EIU, protein content rose within 4 hours, followed by infiltrating leukocytes. EIU AqH p romptly lost its capacity to suppress T-cell proliferation and became mitog enic for T cells. In AqH of EAU, protein and leukocyte content rose at 11 d ays and continued to remain elevated thereafter. Whereas 11-day EAU AqH fai led to suppress T-cell proliferation, AqH at later time points reacquired i mmunosuppressive properties. Injection of OVA into the AC of eyes of mice w ith EAU failed to induce ACAID. CONCLUSIONS. The intraocular inflammation of EIU and EAU disrupted importan t parameters of immune privilege, ranging from breakdown of the blood- ocul ar barrier, to loss of an immunosuppressive microenvironment, to abrogation of ACAID. Because AqH from inflamed EAU reacquired the ability to suppress T-cell proliferation, the authors conclude that the capacity to regulate i mmune expression and inflammation can be a property even of inflamed eyes.