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, CD11bintCD11chiMHCIIhiCD86hi cells increased until 4 weeks with an increase in IFNγhi T cells. In Syn, both CD11bintCD11chiMHCIIhiCD86hi and CD11bhiCD11chiMHCIIhiCD86hi APC subsets increased until 4 weeks with a brief increase in CD69hi T cells at 2 weeks. In Allo, CD11bintCD11chiMHCIIhiCD86hi and CD11bhiCD11chiMHCIIhiCD86hi APC subsets increased until 4 weeks, and an early increase in CD69hi T cells was observed at 2 weeks followed by a late increase in IFNγhi T cells at 4 weeks. The frequency of the IFNγhi T cell subset was positively correlated with the frequency of the CD11bintCD11chiMHCIIhiCD86hi 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.
Highlights
Introduction published maps and institutional affilThe eye is equipped with immune privilege through immunologic ignorance and active immunosuppression [1,2]
To further characterize the antigen-presenting cell (APC) subsets, which were further purified with F4/80 from the ocular surface, an additional experiment was conducted and the mice were sacrificed at 2 weeks (n = 20 mice; 5 per group)
We addressed the time-serial changes of two types of mature APC subsets, including CD11bint CD11chi MHCIIhi CD86hi and CD11bhi CD11chi MHCIIhi CD86hi cells, and CD3+ CD69hi and CD3+ IFNγhi T cells in the ocular surface (Figure 1), which responded to a partial corneal trephination (i.e., PT group) as a quiescent inflammation or to a syngeneic corneal transplantation (i.e., Syn group) as a potent sterile inflammation and to allogeneic corneal transplantation (i.e., Allo group) as an allosensitization (Figures 2 and 3)
Summary
The experiments were serially conducted at one, two, and four weeks. Balb/c female mice (n = 54), which were 7 weeks old, were purchased from Orient Bio Inc. The Balb/c mice were assigned to four groups: (1) control (Ct, n = 3 mice), (2) partial trephination group (PT, n = 5 mice), (3) syngeneic (Syn, n = 5 mice), and (4) allogeneic (Allo, n = 5 mice) corneal transplantation group, with one set for each time point (n = 18 mice/week). To further characterize the APC subsets, which were further purified with F4/80 from the ocular surface, an additional experiment was conducted and the mice were sacrificed at 2 weeks (n = 20 mice; 5 per group). The number of each group in this study was based on a previous study that analyzed the immune cell subsets in a set of corneal transplantations in a murine model [18]
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