The Distribution of Antigen in Lymphoid Tissues following Its Injection into the Anterior Chamber of the Rat Eye

Abstract

Injection of Ag into the anterior chamber (AC) of the eye induces deviant immune responses. It has been proposed that Ag internalized by ocular APCs is presented in a tolerogenic fashion in the spleen. However, the nature and distribution of the Ag-bearing cells in the lymphoid organs remain unclear. Fluorescent-labeled Ag (dextran, BSA) injected into the AC of Lewis rats was detected in the subcapsular sinus of the right submandibular lymph nodes (LNs) and cervical LNs, the marginal zone of the spleen, and the medulla of the mesenteric LNs. In the spleen, Ag-bearing cells were CD1+, CD11b+, ED1+, ED2low, ED3+, CD86low, OX6+, CD11c−, ED5− and in the LNs were CD4+, CD8+, CD80+, and OX41+ suggesting these were lymphoid organ resident macrophages. These Ag-bearing macrophages were located adjacent to CD4+ cells, CD8+ cells, and NK cells in the LNs and spleen and to marginal zone B cells in the spleen. No interaction with γδ T cells was observed. The data demonstrates that Ag derived from the AC of the eye is mainly internalized by resident macrophages in the LNs and spleen which are ideally placed to interact with cells involved in the induction of deviant ocular immune responses. The extensive distribution of Ag in LNs draining the upper airway and gastrointestinal tracts, together with the phenotype of Ag-bearing cells in the lymphoid organs, suggests that Ag leaves the eye predominantly in a soluble form and implies other mechanisms of tolerance may contribute to ocular-specific immune responses.

The Impact of Corneal Allograft Rejection on the Long-Term Outcome of Corneal Transplantation

“…It might occur in the uvea, 23 the conjunctiva-13 associated lymphoid tissue, 24 the draining lymph nodes, 25 or beyond. Antigen may leave 14 the eye as soluble antigen 26 or be carried by mobile accessory cells. 27 have the capacity to cause cell damage, but corneal graft rejection still occurs in animals 10 deficient in CD8+ cells.…”

APCs in the Anterior Uveal Tract Do Not Migrate to Draining Lymph Nodes

“…Note added in proof. While this manuscript was in press, Camelo et al (52) published the results of a study in rats showing that Ag injected into the anterior chamber of the eye is detectable in the draining lymph nodes in the context of APCs that express a cell surface marker typically not present on ocular APCs. Unless the ocular APC has changed its phenotype, the observations are consistent with our conclusions that soluble Ag does not exit from the anterior chamber in the context of an APC enroute to a draining lymph node.…”

Cutting Edge: Membrane Nanotubes In Vivo: A Feature of MHC Class II+ Cells in the Mouse Cornea

“…However, recent studies of bone marrow (BM)-derived cells in the mouse cornea have revealed a network of cells, including CD11c ϩ MHC class II ϩ DCs and CD11b ϩ macrophages (8 -10). These studies have been made possible by the transparency of the cellular and extracellular matrix of this critical refractive layer of the eye and its ready accessibility for both intravital and ex vivo microscopic investigations (11,12). During studies of these cells in corneal whole mounts from wild-type, transgenic, and enhanced GFP (eGFP) chimeric mice we noted the presence of extremely long, fine cellular processes arising from MHC class II ϩ putative DCs in the corneal stroma.…”