T-CELL TRAFFIC AND THE INFLAMMATORY RESPONSE IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

PURPOSE. TO quantify S-antigen-specific (S-Ag) T cells in the retina a fter adoptive transfer, and to evaluate their role in the initiation a nd progress of destructive ocular inflammation in experimental autoimm une uveoretinitis (EAU).METHODS. Lewis rats were administered 10 X 10( 6) S-Ag-specific T cells from the SP35 cell line or 10 X 10(6) concana valin A-stimulated syngeneic spleen cell lymphoblasts labeled with lip ophilic PKH26 fluorescent dye immediately before intravenous inoculati on. Labeled cells in each retina mere counted at various times from 4 to 120 hours after cell transfer by fluorescence microscopic analysis of each dissociated retina. Recipient eyes were examined within the sa me period by light and confocal microscope. RESULTS. SP35 T cells show ed a biphasic distribution in the retina. The first peak of 160 cells/ retina was noted at 24 hours. A steady decline of labeled cells at 48 and 72 hours mas followed by a rapid increase at 96 and 120 hours, Con canavalin A-stimulated, control-labeled cell populations showed an ide ntical peak at 21 hours but a persistent decline thereafter; only two or three T cells were present in each retina at 120 hours. Concurrent inoculation of SP35 cells and nonspecific T cell blasts did not produc e more SP35 cells than control cells in the retina at an) time. Micros copic analysis showed mononuclear cell infiltration of the iris, cilia ry body, and aqueous humor at 48 hours, which intensified rapidly and persisted through 120 hours. Retinal inflammation did not begin until 80 hours. Mononuclear cell adherence to vascular endothelium and periv ascular macrophage infiltration of the innermost layers progressed to edema, and profound destructive inflammation and loss of retinal strat ification were observed at 120 hours. CONCLUSIONS. There is no evidenc e of a blood-ocular or blood-retinal barrier to activated T cell blast s. Autologous S-Ag does not provoke a more rapid entry of specific T c ells at that site. The data confirm that anterior segment inflammation precedes retinal inflammation, even though S-Ag-specific T cells were present in the retina within a few hours after cell transfer. Because S-Ag is clearly present in the retina, delay in antigen presentation at that site may account for the temporal difference between retinal a nd anterior segment inflammation.