Prevention of experimental autoimmune uveoretinitis by monoclonal antibody to interleukin-12.
Experimental autoimmune uveoretinitis (EAU) induced by immunization with interphotoreceptor retinoid-binding protein (IRBP), a retinal self antigen, has been regarded to be a typical T helper type 1 (Th1)-mediated inflammatory disease. In this study, we examined the effect of a neutralizing monoclonal antibody (mAb) to interleukin-12 (IL-12), which has been known to play a critical role in the Th1 differentiation, on the development of EAU. While 9 of 13 control mice developed EAU by the immunization with IRBP, none of 12 mice developed EAU when given anti-IL-12 mAb 1 day before immunization. These mice did not develop EAU even after a rechallenge with IRBP on day 30, indicating that a protective mechanism had been established by the anti-IL-12 treatment. The proliferative response of splenocytes to IRBP in vitro was not significantly impaired, but the production of IL-2 and IFN-gamma was greatly reduced by the anti-IL-12 treatment. Moreover, production of IL-5 and expression of IL-4 mRNA were increased by the anti-IL-12 treatment. Consistently, IgG2a anti-IRBP serum antibodies were decreased and IgG1 were increased. Administration of a neutralizing anti-IL-4 mAb at the time of IRBP rechallenge reversed the protection established by the anti-IL-12 treatment at the primary immunization. These results indicate that the anti-IL-12 treatment at the IRBP priming not only prevented the development of pathogenic Th1 cells, but also induced suppressive Th2 cells that protect the animals from further challenge with the same antigen.
Yokoi
H
H
Department of Ophthalmology, Tokyo Medical College Hospital, Japan.
Kato
K
K
Kezuka
T
T
Sakai
J
J
Usui
M
M
Yagita
H
H
Okumura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D005136:Eye Proteins; D005260:Female; D015870:Gene Expression; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D012173:Retinitis / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D016207:Cytokines; D005136:Eye Proteins; D007074:Immunoglobulin G; D018664:Interleukin-12; D015847:Interleukin-4; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial