Time-Dependent Serial Changes of Antigen-Presenting Cell Subsets in the Ocular Surface Are Distinct between Corneal Sterile Inflammation and Allosensitization in a Murine Model

Abstract

The kinetics of antigen-presenting cells (APCs) vary depending on their resident tissues and the manner of immunization. We investigated the long-term changes in mature APC and T-cell subsets over 4 weeks in the ocular surface in murine models of corneal quiescent or potent sterile inflammation, and allosensitization using partial (PT), syngeneic (Syn), and allogeneic (Allo) corneal transplantation. In PT, CD11b^intCD11c^hiMHCII^hiCD86^hi cells increased until 4 weeks with an increase in IFNγ^hi T cells. In Syn, both CD11b^intCD11c^hiMHCII^hiCD86^hi and CD11b^hiCD11c^hiMHCII^hiCD86^hi APC subsets increased until 4 weeks with a brief increase in CD69^hi T cells at 2 weeks. In Allo, CD11b^intCD11c^hiMHCII^hiCD86^hi and CD11b^hiCD11c^hiMHCII^hiCD86^hi APC subsets increased until 4 weeks, and an early increase in CD69^hi T cells was observed at 2 weeks followed by a late increase in IFNγ^hi T cells at 4 weeks. The frequency of the IFNγ^hi T cell subset was positively correlated with the frequency of the CD11b^intCD11c^hiMHCII^hiCD86^hi subset, indicating the existence of APC-T cell interaction in the ocular surface. Together, the results indicate that allosensitization in mature APCs leads to T-cell activation in the ocular surface, whereas sterile inflammation merely induces a brief and non-specific T-cell activation in the ocular surface.

Keywords: allograft; allosensitization; antigen-presenting cell; cornea; dendritic cell; macrophage; sterile inflammation; syngraft.