Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells

PURPOSE: The presence of antigen-presenting cells (APCs) such as Langerhans cells (LCs), an epithelial form of dendritic cells (DCs), in corneal tissue is critical for generation of immune responses, including graft rejection and herpetic keratitis. The purpose of this study was to characterize the distribution and major histocompatibility complex (MHC) antigen expression of corneal LCs. METHODS: Normal and inflamed corneas were excised from BALB/c mice, and immunofluorescence staining for CD11c, CD11b, CD45, CD80 (B7.1), CD86 (B7.2), CD3, and MHC class II (Ia) was performed by confocal microscopy on wholemount corneal epithelium. RESULTS: CD11c(+) MHC class II-positive LCs were found in the limbus and corneal periphery, but not in the center of the normal cornea. These cells were CD45 positive, exhibiting bone marrow derivation, and CD3 and CD11b negative, confirming a DC lineage. Additionally, these cells were CD80 and CD86 negative, reflecting an immature phenotype. In the central and paracentral areas, however, significant numbers of CD11c(+) LCs were detected that expressed no MHC class II. It is important to note that although the density of the LCs declined from the limbus toward the center of the cornea, they were always present. In the inflamed cornea, the expression of MHC class II and costimulatory molecules CD80 and CD86 was significantly enhanced, and present in all parts of the cornea, in contrast to the normal cornea. CONCLUSIONS: The present study demonstrates for the first time the phenotype and distribution of MHC class II-negative LCs in the murine corneal epithelium. In the inflamed cornea, the LCs become activated as reflected by expression of B7 costimulatory markers. These changes in activation markers may provide additional information for devising novel immunomodulatory strategies.