Localization and characterization of major histocompatibility complex class II-positive cells in the posterior segment of the eye: implications for induction of autoimmune uveoretinitis

Abstract

Purpose: To identify potential antigen-presenting cells in the choroid and retina of the normal rat eye, with a view to proposing a role for such cells in the induction and perpetuation of experimental autoimmune uveoretinitis, a model of human uveoretinal inflammation.

Methods: Immunohistochemical and electron microscopic studies using a panel of monoclonal antibodies were performed on frozen sections of the perfused-fixed normal Lewis rat eye, choroid whole mounts, and cytospin preparations of cells harvested from choroid/ciliary body explant cultures. In addition, time-lapse video recordings of migratory uveal tract cells in culture were taken.

Results: No major histocompatibility complex class II-positive cells were found in the normal Lewis rat retina. However, at least three populations of potential antigen-presenting cells were found in the uveal tissues of the eye: classical dendritic cells expressing high levels of major histocompatibility complex class II antigen; resident dendritiform macrophages, which were negative for major histocompatibility complex class II antigen, but expressed specific macrophage markers (ED2); and blood-borne macrophages (ED1) that had emigrated from the vasculature into the tissue compartment. In addition there were small numbers of cells expressing novel markers such as markers usually found only on macrophage subsets in splenic tissue (ED3) and a recently described marker for veiled dendritic cells (OX62). Dendritic cells and resident dendritiform macrophages closely interacted with each other and with tissue cells, particularly retinal pigment epithelial cells.

Conclusions: The posterior uveal tract is richly populated with classical dendritic cells expressing constitutive high levels of major histocompatibility complex class II antigen. There are also several types of macrophages with the potential to modulate immune responses in the posterior segment. Interactions among these cells and with resident tissue cells such as retinal pigment epithelial cells are probably central to the initiation of (auto)immune responses in the posterior segment of the eye.