Amelioration of Experimental Autoimmune Uveoretinitis by Pretreatment with a Pathogenic Peptide in Liposome and Anti-CD40 Ligand Monoclonal Antibody

• Published in: The Journal of immunology (1950) 2000-09, Vol.165 (6), p.2962-2969
• Main Authors: Namba, Kenichi, Ogasawara, Kazumasa, Kitaichi, Nobuyoshi, Morohashi, Taiki, Sasamoto, Yoichi, Kotake, Satoshi, Matsuda, Hidehiko, Iwabuchi, Kazuya, Iwabuchi, Chikako, Ohno, Shigeaki, Onoe, Kazunori
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Animals; Antibodies, Monoclonal - administration & dosage; Autoimmune Diseases - etiology; Autoimmune Diseases - pathology; Autoimmune Diseases - prevention & control; Cattle; CD40 Antigens - metabolism; CD40 Ligand; CD40L protein; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Drug Carriers; Epitopes, T-Lymphocyte - immunology; experimental autoimmune uveoretinitis; Eye Proteins; Female; Immunosuppressive Agents - administration & dosage; Injections, Subcutaneous; Ligands; Liposomes; Lymphocyte Activation - immunology; Membrane Glycoproteins - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Peptide Fragments - administration & dosage; Retinitis - etiology; Retinitis - immunology; Retinitis - pathology; Retinitis - prevention & control; Retinol-Binding Proteins - administration & dosage; T-Lymphocytes - immunology; Th1 Cells - immunology; Th1 Cells - metabolism; Time Factors; Uveitis - etiology; Uveitis - immunology; Uveitis - pathology; Uveitis - prevention & control
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.6.2962

We have defined a peptide K2 (ADKDVVVLTSSRTGGV) that corresponds to residues 201-216 of bovine interphotoreceptor retinoid-binding protein and induces experimental autoimmune uveoretinitis (EAU)4 in H-2Ak-carrying mice (H-2Ak mice). In this study, we attempted to ameliorate EAU in the H-2Ak mice without nonspecific suppression of T cell responses. Preceding s.c. administration of liposomes including K2 (liposomal K2) specifically inhibited subsequent generation of T cell response to K2. The same result was obtained with a combination of OVA323-339 peptide and the OVA-specific TCR-transgenic T cells. It was suggested that the inhibition was mainly attributed to peripheral anergy induction of T cells specific for the peptide Ag, although specific cell death might also be involved in the inhibition. Pretreatment with liposomal K2 also considerably abolished IFN-gamma production but not IL-4 production. The specific inhibitory effect of the pretreatment with liposomal peptide was augmented by a simultaneous administration of anti-CD40 ligand (anti-CD40L) mAb. Moreover, it was shown that the pretreatment with liposomal K2 reduced both the incidence and severity of the subsequent K2-induced EAU, and the simultaneous administration of anti-CD40L mAb augmented this preventive effect by liposomal K2. Our findings demonstrate that the s.c. administration of liposomal pathogenic peptide and anti-CD40L mAb can be applied to preventing autoimmune diseases without detrimental nonspecific suppression of T cell responses.