Peptide-mediated suppression of experimental autoimmune uveoretinitis in mice: development of a peptide vaccine.
Experimental autoimmune uveoretinitis (EAU) is an animal model of antigen-specific, Th cell-mediated, organ-specific autoimmune disease. EAU is induced by immunization of B10.A mice with interphotoreceptor retinoid-binding protein (IRBP). Pre-treatment with synthetic peptide 518-529 derived from IRBP prevented IRBP-mediated EAU. This was accompanied by augmentation of the IRBP-specific IgG1 antibody (Th2) response and down-regulation of the IRBP-specific IgG2a (Th1) response. Consistent with this is the observation that two of two T cell lines established from p518-529-primed mice produced Th2-type cytokines (IL-4 and IL-10), whereas three of three T cell lines obtained from IRBP-primed mice produced Th1-type cytokines (IL-2 and IFN-gamma). Together this suggests the possibility that p518-529 priming causes a shift from a Th1-to a Th2-dominated immune response, thereby playing a pivotal role in the prevention of IRBP-mediated EAU. Furthermore, co-transfer of cells from a CD4+ p518-529-specific T cell line prevented the development of EAU after adoptive transfer of spleen cells from mice with EAU into normal mice. These findings contribute to our understanding of the mechanism of EAU, particularly with respect to the down-regulation of Th1-initiated inflammation, and may prove valuable for designing a peptide vaccine for EAU in the future.
Kezuka
T
T
Department of Ophthalmology, Tokyo Medical College Hospital, Japan.
Sakai
J
J
Yokoi
H
H
Takeuchi
M
M
Okada
A
A
Taguchi
O
O
Usui
M
M
Mizuguchi
J
J
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000737:chemistry / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D012173:Retinitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000099214:Retinol-Binding Proteins, Interstitial
D001323:Autoantibodies; D005136:Eye Proteins; D007074:Immunoglobulin G; D010455:Peptides; D012177:Retinol-Binding Proteins; D014614:Vaccines, Synthetic; D000099214:Retinol-Binding Proteins, Interstitial