摘要:

Experimental autoimmune uveoretinitis (EAU) can be induced in susceptible strains of rats and mice by immunization with purified retinal antigens, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of major histocompatibility complex (MHC) vs. non-MHC genes in the control of susceptibility to ocular autoimmunity, using the mouse and the rat EAU models. It was shown that EAU expression in mice requires both a susceptible MHC haplotype and a“permissive”genetic background. MHC control of susceptibility was tentatively mapped to the I-A subregion in H-2k. I-Ekexpression appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine“permissiveness”or“nonpermissiveness”of a particular genetic background, as studied in mice and rats, may include diverse genetic mechanisms spanning regulation of cytokines, hormones, vascular effects and the T cell repertoire. Taken together, the data suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background.

ISSN:0271-3683    

DOI:10.3109/02713689208999515

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Efficacy of a new immunosuppressive agent, FK506, in refractory uveitis was studied in 8 patients: 5 with Behcet's disease and 3 with idiopathic retinal vasculitis. The agent was given by oral administration every 12 hours. The previous therapy with systemic corticosteroids or immunosuppressive agents including cyclosporine failed to subside uveitis in these cases. During the observation period of 21.6±7.8 weeks (mean±SD) under FK506 at doses with 0.05, 0.1, 0.15 or 0.2 mg/kg/day, the visual acuity was increased in 44% of treated eyes, unchanged in 44% and decreased in 12%. The inflammatory activity in the ocular fundus was improved in 69% and unchanged in 6% of treatead eyes. The effects of FK506 on uveitis by the criteria of improvement of visual acuity and uveitis activity was dose-dependent: 0.05 and 0.1 mg/kgday were ineffective but 0.15 and 0.2 mg/kg/day were effective in most cases. One patient with Behcet's disease converted from cyclosporine developed moderate renal impairment in 4 weeks under FK506 and the therapy was discontinued in 8 weeks, though the uveitis activity as well as visual acuity was markedly improved. Other 7 cases had no side effect of FK506. Although the number of cases was small and observation period was short, the present clinical data indicate that FK506 is effective to treat refractory uveitis.

ISSN:0271-3683    

DOI:10.3109/02713689208999516

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Experimental Autoimmune Uveitis (EAU) was induced by immunization with bovine interphotoreceptor retinoid binding protein (IRBP) in B10.A mice. The experiments were performed to evaluate whether Anterior Chamber Associated Immune Deviation (ACAID) can be induced by IRBP when injected intracamerally. The results indicate that anterior chamber (AC) injection of IRBP impaired the development of IRBP-specific delayed hypersensitivity and prevented the expression of EAU following immunization with IRBP-CFA. Adoptive transfer of spleen cells obtained from mice that received IRBP into AC suppressed EAU, whether administered prior to or after the uveitogenic regimen. Most important, IRBP-specific suppressor cells from AC-IRBP treated mice when injected into IRBP-EAU mice suppressed and eliminated already established intraocular inflammation. IRBP-specific, ACAID-inducing suppressor T cells act on the efferent limb of the immune response, and represent ideal modalities for treating already established EAU.

ISSN:0271-3683    

DOI:10.3109/02713689208999517

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We previously demonstrated that mercuric chloride (HgCl2) injected-(Lewis x Brown-Norway) F1rats are protected against experimental autoimmune uveoretinitis (EAU) induced by active immunization with the retinal S-antigen (S-Ag). To better understand the mechanisms of the protection promoted by HgCl2, we studied the effect of HgCl2-induced autoimmune disease on transferred EAU. We demonstrate herein that HgCl2has no effect on adoptively transferred EAU. Therefore, the HgCl2-induced autoimmune disease does not affect effector S-Ag specific T cells activated in vitro but acts at an earlier stage.

ISSN:0271-3683    

DOI:10.3109/02713689208999518

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are CD4+ T cell mediated inflammatory diseases of the retina and uveal tract of the eye and the pineal gland respectively. They can be induced in experimental animals by immunization with several well characterized retinal autoantigens. We induced a mild to moderate EAU and EAP in Lewis rats by immunization with phosducin, a 33K retinal phosphoprotein which is involved in the phototransduction of vision. In contrast to the severe EAU induced by other retinal antigens like S-antigen (SAg) or interstitial retinoid binding protein (IRBP), the clinical disease was late in onset, low grade in severity and predominantly affected the posterior segment of the eye. Our study demonstrates that another photoreceptor cell protein, phosducin, is capable of eliciting EAU and EAP.

ISSN:0271-3683    

DOI:10.3109/02713689208999519

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

A full-length cDNA clone to human S-antigen (HS-ag) was isolated fromγgt 10 human retinal library and expressed as a fusion protein with glutathione S-transferase (GST) inE. Coli.Uveitogenicity and immunogenicity of recombinant GST-HS-ag fusion protein and native HS-ag were compared in EAU-susceptible Lewis rats.Recombinant HS-ag was found less uveitogenic than native HS-ag. Animals inoculated with recombinant HS-ag developed EAU on day 17, three days later than those inoculated with native HS-ag, the incidence of the disease was reduced from 80% to 58% and the score of clinical severity reduced from 2.2 to 1.3 points respectively. In contrast, rGST-HS-ag was more immunogenic than native HS-ag as it elicited four times higher levels of antibodies which reacted specifically with both antigens.

ISSN:0271-3683    

DOI:10.3109/02713689208999520

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

S-antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU) in rats can be suppressed by injecting the mouse monoclonal antibody (mAb) S2D2 or a polyclonal rat anti-idiotype S2D2 (anti-Id S2D2) antibody, the internal image of the epitope of S-Ag recognized by mAb S2D2. This epitope located in amino acids 40–50 of bovine S-Ag (peptide S2), displays an homology with a sequence of human tumor necrosis factor alpha (hTNFα) (peptide RRAN) which is also recognized by S2D2. (Stiemer et al., this symposium). We show that one injection of S2D2 at the time of immunization with S-Ag suppressed EAU and modulated the production of antibodies against peptides of bovine or human S-Ag containing the S2 epitope and against peptide RRAN. Immunization against anti-Id S2D2 stimulated antibody production to peptide S2 and RRAN and inhibited EAU. These data suggest that disease suppression could be related to the production of antibodies against the S-Ag/TNFαcommon epitope.

ISSN:0271-3683    

DOI:10.3109/02713689208999521

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Using a Lewis rat model of IRBP induced EAU, we have examined the progress of leucocytes infiltrating the uveitic eye. APAAP and dual immunofluorescence were used to show that ED7 and 8 (CD11b/CD 18) positive monocytes, W3/25 and OX8 (CD4 and CD8) lymphocytes were prominant in the initial inflammatory exudate around the retinal vessels and in the choroid. ED1 positive monocytes were also observed in the choroid. As disease progressed, these cells moved into the inner retina, vitreous and ROS. ED8 positive cells were the first to appear in the ROS. This was followed by the later appearance of ED2 tissue macrophages in the vitreous and ED3 inflammatory macrophages in the vitreous and ROS.

ISSN:0271-3683    

DOI:10.3109/02713689208999522

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

S-antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU) was suppressed in Lewis and PVG rats by treatment beginning 4 days post immunization with prazosin, a specificα1-adrenergic receptor antagonist. A significant suppression of EAU was observed at clinical and histological levels in both treated groups compared to a severe EAU which developed in controls. Fluorescein angiography showed no leakage of dye from the optic disc of a treated PVG rat presenting no ocular inflammation by clinical examination. The treatment had no effect on the titer of anti-S-Ag antibodies. Perivascular infiltrates of T-lymphocytes and macrophages together with alterations of blood-retinal barrier permeability are early events in EAU. Prazosin, by acting on the vascularα1-adrenoreceptors, inhibits vasospasm, preserves blood-retinal-barrier integrity and prevents vascular edema and early inflammatory cell infiltration observed in EAU.

ISSN:0271-3683    

DOI:10.3109/02713689208999523

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Acute anterior uveitis (AAU) is strongly associated with the genetic marker and cell membrane protein HLA-B27. Although also other genetic factors must play a pathogenetic role, the HLA-class I molecule B27 is up to now the only hold. The normal task of HLA class I molecules is to present endogenous, mostly viral, peptides to receptors on cytotoxic T cells. It is possible that HLA molecules at the cell surface serve as viral receptors. Human cytomegalovirus (HCMV) particles have been found to bindβ2m. This might promote infectivity by a binding to HLAα-chains on cell membranes. We studied this mechanism using mouse fibroblasts transfected for human HLA class I molecules. Susceptibility of these cells for HCMV was compared by measuring of HCMV immediate early antigen (IEA) expression. Earlier we observed that cells transfected with HLA-B27α- chains andβ2m were significantly more infected than cells expressing HLA-A2 +β2m or HLA-B7 or HLA-B27 withoutβ2m. However, studying another four, separately transfected, cell lines, all expressing HLA-B27 andβ2m, three of the five B27 cell lines showed low IEA levels. The degree of infectivity was independent of the degree of B27 expression. These results do not support the previous suggestion that HLA-B27 might act as an HCMV receptor.

ISSN:0271-3683    

DOI:10.3109/02713689208999524

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor