Class II major histocompatibility complex (Ia) antigen-bearing dendritic cells within the iris and ciliary body of the rat eye: distribution, phenotype and relation to retinal microglia

Abstract

The density, distribution and surface phenotype of dendritic cells (DC) and macrophage populations within the ciliary body and iris of Wistar Furth rats were studied by a combination of flat mounting, tangential sectioning, pre-embedding fixation, with a single and double immunohistochemical techniques. Monoclonal antibodies included anti-Ia (OX6) and other dendritic cell/macrophage (ED1 and ED8) or mature tissue macrophage markers (ED2). Single and double staining revealed a network (approximately 400 cells/mm2) of Ia+ cells within the epithelium of the ciliary processes with the morphological and surface phenotypic characteristics of DC populations in other tissues. A minor proportion of DC co-expressed ED1 and ED8, but not ED2. In contrast the immunopositive cells in the lamina propria displayed a more generalized phenotype, including ED2 expression, and pleiomorphic morphology suggesting a preponderance of cells of macrophage lineage. Flat mounts of iris revealed a remarkably regular network of Ia+ DC at a density of 450 cells/mm2. The network of DC in the ciliary epithelium terminated at the cilioretinal junction where they formed a continuous syncytium with retinal microglia which did not display Ia staining. The demonstration of networks of cells with relevant morphological and phenotypical properties of professional antigen-presenting cells at strategic locations within the eye has important implications in relation to ocular immune regulation and on the theories of the mechanism of anterior chamber-associated immune deviation (ACAID). Namely, until now it has been assumed that 'immune privilege' in the anterior chamber of the eye is partly a consequence of there being a paucity of class II+ cells in the surrounding tissues. Dendritic cells in the eye may function as antigen-presenting cells, sampling endogenous and exogenous intraocular antigens and possibly migrating from the eye to draining lymphoid organs (the spleen) where they may generate systemic immune responses. Equally dendritic cells could potentially regulate local immune responses for example in various forms of autoimmune uveoretinal inflammatory disease.