Jared E. Knickelbein^1,3, Simon C. Watkins^2,4, Paul G. McMenamin⁷ and Robert L. Hendricks^3-6

¹Medical Scientist Training Program, ²Center for Biologic Imaging, ³Departments of Ophthalmology, ⁴Cell Biology and Physiology, ⁵Immunology, ⁶Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ⁷School of Anatomy and Human Biology and the Lions Eye Institute, University of Western Australia, Crawley, Western Australia, Australia.

Abstract

The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD11c promoter  (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c⁺ dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 µm in length and traverse up 20 µm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c^-CD11b⁺ putative macrophages that express low levels of MHC class II. Finally, MHC class II^-CD11c^-CD11b⁺ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma.