Resident and infiltrating immune cells in the uveal tract in the early and late stages of experimental autoimmune uveoretinitis

Abstract

Purpose: To investigate the dynamics of resident and infiltrating immune cells in the choroid and iris during the early and late stages of experimental autoimmune uveitis (EAU) in Lewis rats.

Methods: Uveoretinitis was induced by footpad injection of crude retinal extract and complete Freund's adjuvant with concurrent intraperitoneal injection of Bordetella pertussis. Five experimental (EAU) and five control animals (adjuvant alone) were studied at days 5, 7, 9, 11 (prodromal stage) and 42 (late stage) after immunization. Five normal animals and five animals injected with B. pertussis alone served as further controls. Immunohistochemical localization of resident macrophages, major histocompatibility complex class II (Ia)+ dendritic cells (DC), infiltrating mononuclear cells, and T cells was performed on wholemounts of isolated choroidal and iris tissue.

Results: Double immunolabeling confirmed the presence of distinct networks of macrophages (591 +/- 52 cells/mm2) and DC (746 +/- 38 cells/mm2) in the rat choroid. No marked qualitative and quantitative changes were observed in the density or morphologic appearance of ED2+ resident tissue macrophages in the choroid and iris before clinical onset of ocular disease. On day 11, infiltration of ED1+ monocytes had occurred in the iris but not in the choroid; however, marked infiltration of T cells was evident in both choroid (286 +/- 161 cells/mm2) and iris (196 +/- 72 cells/mm2). The total density of Ia+ cells was significantly elevated in the choroid (1152 +/- 192 cells/mm2) at day 11, and small, round Ia+ cells were two to three times more frequent than normal at both sites. The density of T cells and Ia+ cells remained significantly elevated in the choroid and iris in the late stages of EAU.

Conclusions: These data suggest resident uveal tract macrophages undergo no significant alteration in density in the early stages of EAU and that the earliest site of mononuclear cellular infiltrate in EAU occurs in the iris. The increased total density of Ia+ cells in the choroid on day 11 and the presence of significantly increased numbers of small, round Ia+ cells in the iris and choroid may represent increased trafficking of DC in the eye during uveoretinitis. Furthermore, the raised numbers of Ia+ cells, concurrent with the influx of T cells, suggests Ia+ DC and macrophages may act as local antigen-presenting cells in the induction of uveoretinitis.