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Role of T-cell receptor V beta 8.3 peptide vaccine in the prevention of experimental autoimmune uveoretinitis
Authors:Zhang Rui  Yang Pei-zeng  Wu Chang-you  Jin Hao-li  Li Bing  Huang Xiang-kun  Zhou Hong-yan  Gao Yang  Zhu Lian-xiang  Kijlstra Aize
Institution:1. Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou 510060, China
2. Department of Immunology, Sun Yat-sen University, Guangzhou 510089, China
3. Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou 510060, China;Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
4. Animal Sciences Group, Wageningen University and Research Centre, Lelystad; Eye Research Institute Maastricht; and Department of Ophthalmology, Academic Medical Centre,University of Amsterdam, the Netherlands
Abstract:BACKGROUND: T-cell receptor (TCR) plays an important role in the development of autoimmune diseases. Recently, it was reported that immunization of animals with TCR peptide derived from the pathogenic cells could prevent autoimmune diseases. The aim of this study was to investigate whether vaccination with a synthetic peptide from the hypervariable region of TCR V(beta) 8.3, an experimental autoimmune uveoretinitis (EAU)-associated gene, was able to prevent the disease. METHODS: EAU was induced in Lewis rats by immunization with IRBP R16 peptide emulsified in complete Freund's adjuvant (CFA). The clinical and histological appearances were scored. Delayed type hypersensitivity (DTH) and lymphocyte proliferation were detected. Cytokine levels of aqueous humour, supernatants of cells from spleen and draining lymph nodes were measured by enzyme linked immunosorbent assay (ELISA). Gene expression of TCR V(beta) 8.3 on CD(4)(+) T cells was examined by real time quantitative polymerase chain reaction (PCR). RESULTS: After vaccination, the intraocular inflammation was significantly mitigated, antigen specific DTH and lymphocyte proliferation responses were suppressed, interleukin (IL)-2 in aqueous humour, interferon (IFN)-gamma and IL-2 produced by the spleen and draining lymph node cells were significantly decreased, whereas the production of IL-4 and IL-10 were increased. The response of draining lymph node cells to TCR V(beta) 8.3 peptide was enhanced after vaccination. Inoculation with CFA alone did not affect the severity of EAU and the above parameters. The suppression of EAU was much stronger in the group of four fold inoculations than the group of two fold inoculations. The expression of TCR V(beta) 8.3 gene was significantly reduced in the group of fourfold inoculations. CONCLUSION: Vaccination with the synthetic TCR V(beta) 8.3 peptide could remarkably inhibit the development of EAU.
Keywords:uveoretinitis  autoimmune  T-cell receptor  peptide vaccine
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