Peritoneal exudate cells treated with calcitonin gene-related peptide suppress murine experimental autoimmune uveoretinitis via IL-10.
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.
Kezuka
Takeshi
T
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan. tkezuka@tokyo-med.ac.jp
Takeuchi
Masaru
M
Keino
Hiroshi
H
Usui
Yoshihiko
Y
Takeuchi
Aya
A
Yamakawa
Noriyuki
N
Usui
Masahiko
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D012173:Retinitis / Q000188:drug therapy / Q000276:immunology*; D013156:Splenectomy; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016753:Interleukin-10; D015740:Calcitonin Gene-Related Peptide