"Corneal Nerves, CD11c+ Dendritic Cells and Their Impact on Ocular Immune Privilege"

Abstract

The eye and the brain have limited capacities for regeneration and as such, immune-mediated inflammation can produce devastating consequences in the form of neurodegenerative diseases of the central nervous system or blindness as a result of ocular inflammatory diseases such as uveitis. Accordingly, both the eye and the brain are designed to limit immune responses and inflammation - a condition known as "immune privilege". Immune privilege is sustained by physiological, anatomical, and regulatory processes that conspire to restrict both adaptive and innate immune responses.

Keywords: contrasuppressor cells; cornea; dendritic cells; immune privilege; nerves.

Figure 1

Germinating seedling in the anterior chamber of an eight year-old boy following 10 weeks of ocular pain. The vermiform object was extirpated and identified by a botanist to be a seedling of a dicotyledonous plant. Reproduced from Abel (1) with permission from Archives Ophthalmology.

Figure 2

Four organ systems are required for the induction of ACAID. Removal of the eye, spleen, or thymus within 3 days of injecting antigen into the anterior chamber prevents the induction of ACAIDS. Chemical sympathectomy prior to injecting antigens into the anterior chamber also prevents ACAID. BCR, B cell receptor. Reproduced from Niederkorn (9) with permission from Nature Publishing Group.

Figure 3

Shallow circular incisions of the cornea in one eye abolishes ACAID in both eyes. 360° corneal incisions were placed in left (OS) eyes of BALB/c mice 14 days prior to application of C57BL/6 corneal allografts to the right (OD) eyes. (Modified from Paunicka et al. (29).

Figure 4

Sympathetic loss of immune privilege is the result of an axis involving ocular surface CD11c⁺ DCs, corneal nerves, and the elaboration of substance P (SP). (A, B) MHC class II⁺ DCs (including CD11c⁺ DCs) reside at the interface between the corneal allograft and the graft bed. (C) Severing corneal nerves with a trephine elicits the release of SP that converts resident CD11c⁺ DCs to contrasuppressor (CS) cells that disable CD4⁺CD25⁺ Tregs. Reproduced from Niederkorn (39) with permission from Invest Ophthalmol Vis Sci.