Introduction The local ocular microenvironment is critically important in maintaining ocular health and limiting inflammation. Mechanisms for immunologic regulation in the eye are not completely understood but may involve active suppression or immune down-regulation. The B7-CD28 superfamily, including the ICOS (inducible T cell costimulator) and the PD-1 (programmed death gene 1) pathways are of particular interest because of their negative regulatory effects on T cell activity. We examined the expression of the receptors and ligands for ICOS and PD-1 in the murine ocular microenvironment both in normal eyes and in different stages of active intraocular inflammation.
Hypothesis We hypothesized that ICOS, ICOS-L, PD-1, and PD-L2 expression would increase during acute uveitis because their expression would provide additional signals to dampen the intraocular immune response. We also expected that PD-L1 would be constitutively expressed, but that its levels would decrease during acute inflammation.
Methods Uveitis was induced in mice using the uveitogenic IRBP 161-180 peptide in CFA. Normal mice and mice immunized solely with CFA were also evaluated in this study. Eyes and thymus were harvested on days 0, 11, 21, and 31 for histopathologic grading and immunohistochemical evaluation. Lymphocyte proliferation assays were performed using spleen cells at the same time points in order to measure antigen specific responses.
Results Constitutive expression of PD-1 was observed in the retina of normal mice. PD-1 expression was stable during active intraocular inflammation. In contrast, neither PD-L1 nor PD-L2 were observed in normal eyes. However, during the active inflammatory uveitic phase, PD-L1 and PD-L2 expression were observed in the eyes. ICOS and ICOS-L expression were not observed in any of the eyes.
Conclusiion Expression of PD-1 has not been previously reported in the eye. The role for active expression of this protein is not yet understood, but it may be involved in ocular immune privilege. These studies support a role for both PD-L1 and PD-L2 expression during acute uveitis, however identification of the cell type(s) that express these ligands is currently in progress.
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