title: Staphylococcal enterotoxin B is involved in aggravation and recurrence of murine experimental autoimmune uveoretinitis via Vbeta8+CD4+ T cells.
abstract: Endogenous uveitis is a common cause of visual disability and blindness. The etiology of uveitis remains largely unknown but reasonable etiologic factors include infections. Superantigens are regarded as one of the leading causes of infectious etiology in autoimmune disease. However, the role of superantigens in uveitis remains unclear. In the present study, we investigated the effect of Staphylococcal enterotoxin B (SEB), a member of the superantigens, using an experimental model of autoimmune uveoretinitis (EAU). C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein (IRBP) peptide, and the severity of EAU disease was scored. Vehicle (PBS) alone or SEB dissolved in PBS was administered by intravenous injection on post-immunization day 10 or on post-immunization day 24. In addition, a systemic immune response study was performed to address the effects of SEB on systemic immunity. EAU was aggravated significantly by the injection of SEB at post-immunization day 10. Furthermore, relapse was induced by the injection of SEB at day 24. On the other hand, SEB injection without IRBP peptide immunization elicited no inflammatory changes in the uvea or retina. Furthermore, SEB enhanced not only the IRBP-specific T-cell proliferative responses but also IFN-gamma and IL-17 production. Moreover, the intraocular expression levels of these cytokines was also enhanced by SEB injection. Both anti-CD4 and -Vbeta8 Ab administration suppressed disease aggravation and the enhancement of IRBP-specific T-cell responses caused by SEB. These results suggest that SEB is involved significantly in the aggravation or recurrence of endogenous uveitis through activation of autoreactive uveitogenic T cells.
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kohno
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Imanishi
authors.forename: Saburo
authors.initials: S
authors.lastname: Saito
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000494:pharmacology*; D005136:Eye Proteins / Q000276:immunology; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012008:Recurrence; D012173:Retinitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D014605:Uveitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D005136:Eye Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012177:Retinol-Binding Proteins; D018089:Superantigens; D000099214:Retinol-Binding Proteins, Interstitial; C031818:enterotoxin B, staphylococcal