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(int)CD11c(hi)MHCII(hi)CD86(hi) cells increased until 4 weeks with an increase in IFN gamma(hi) T cells. In Syn, both CD11b(int)CD11c(hi)MHCII(hi)CD86(hi) and CD11b(hi)CD11c(hi)MHCII(hi)CD86(hi) APC subsets increased until 4 weeks with a brief increase in CD69(hi) T cells at 2 weeks. In Allo, CD11b(int)CD11c(hi)MHCII(hi)CD86(hi) and CD11b(hi)CD11c(hi)MHCII(hi)CD86(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 IFN gamma(hi) T cells at 4 weeks. The frequency of the IFN gamma(hi) T cell subset was positively correlated with the frequency of the CD11b(int)CD11c(hi)MHCII(hi)CD86(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.