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Peritoneal Exudate Cells Treated with Calcitonin Gene-Related Peptide Suppress Murine Experimental Autoimmune Uveoretinitis via IL-10¹

Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan

Immunization with retinal Ag induces experimental autoimmune uveoretinitis (EAU) in mice. We investigated the suppression of murine EAU by peritoneal exudate cells (PEC) cultured with calcitonin gene-related peptide (CGRP). PEC derived from mice were treated with CGRP and residues 1–20 of human interphotoreceptor retinoid-binding protein (hIRBP 1–20). The hIRBP 1–20-immunized mice were injected i.v. with PEC treated with CGRP and hIRBP 1–20. After immunization, Ag-specific delayed hypersensitivity (DH) was measured and EAU was assessed histopathologically. Both EAU- and Ag-specific DH were suppressed by injection of PEC treated with CGRP (100 ng/ml) and hIRBP 1–20. However, hIRBP 1–20-mediated EAU was not suppressed by injection of PEC treated with CGRP and BSA. Both EAU- and Ag-specific DH were not suppressed by injection of PEC treated with CGRP and hIRBP 1–20 into splenectomized mice. In mice adoptively transferred spleen cells from hIRBP 1–20-immunized mice, EAU was also suppressed by injection of CGRP-treated PEC. EAU was markedly inhibited in hIRBP 1–20-immunized mice adoptively transferred T cells obtained from mice injected with hIRBP 1–20-pulsed, CGRP-treated PEC. Furthermore, EAU- and Ag-specific DH were not suppressed by injection of PEC treated with CGRP and hIRBP 1–20 when the recipient mice were given anti-IL-10 Ab i.p., or when the PEC were derived from IL-10 knockout mice. The present results indicate that PEC treated with CGRP suppress murine EAU in an Ag-specific manner, even in the efferent phase, and IL-10 secreted from PEC might play an important role in the CGRP-mediated suppression of murine EAU.

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