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Preliminary Study on the Expression and Role of CD4~+ CD25~+ Regulatory T Cells in Uveitis

Author: TangHong
Tutor: HuiYanNian；CaiLi
School: Fourth Military Medical University
Course: Ophthalmology
Keywords: Uveitis CD4 ~ CD25 ~ regulatory T cells CTLA-4 Cytokines
CLC: R773
Type: Master's thesis
Year: 2008
Downloads: 101
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Abstract

Objective: uveitis is a common eye disease, is a group of inflammatory lesions involving the uvea, retina, retinal vessels and vitreous, often involving the eyes, easy to repeated attacks, blinding common diseases. Complex etiology and pathogenesis is unclear, there is no ideal treatment method. In recent years, with the development of molecular biology and immunology, the growing awareness of the uveitis is an organ-specific autoimmune disease, more and more studies confirm the immunological mechanisms account for an important role in its pathogenesis. Generally believed that a variety of uveitis are considered for specific eye protein antigen-specific T cell-mediated autoimmune reactions, wherein the T cells may play a central role in the pathogenesis of uveitis. A variety of cytokines such as IFN-γ, TNF-α, IL-10, IL-1, TGF-β, chemokines and their receptors are also involved in the pathogenesis of uveitis. But on its specific pathogenesis is not very clear, and further study the pathogenesis and immunology to explore new immunological treatments for uveitis important. CD4 CD25 regulatory T cells is to regulate one of the subsets of T cells, inhibition of conventional T cell activation through inhibition of autoreactive T cells in the immune response, and to promote the secretion of inhibitory cytokines, while maintaining the machine itself play an important role in the occurrence of autoimmune diseases. Regulatory T cells in CD4 CD25 expression and role in uveitis research focuses on the animal model of experimental autoimmune uveoretinitis (EAU). Several studies have shown that CD4 CD25 regulatory T cells play an important role in the EAU, adoptive transfer of such cells to the EAU mice can play a therapeutic role, provides a new way of thinking for the treatment of uveitis. However, fewer CD4 CD25 cell expression and the role of research in uveitis patients. Therefore, we study was designed to: 1 expression levels in peripheral blood CD4 CD25high Treg cells by detecting different severity in patients with uveitis explore the role of CD4 CD25high Treg cells in the pathogenesis of uveitis; 2 by the simultaneous detection of CD4 intracellular IFN-γ, TNF-α and IL-10 cytokines its mononuclear cell culture supernatant cytokine expression, and analysis of the expression of CD4 CD25high regulatory T cells expressing the relationship, further research uveitis immunology, pathogenesis, and to investigate the mechanism of CD4 CD25high Treg cells might play a regulatory role in the pathogenesis of uveitis. Method: 1. Selected healthy controls 30 cases of 16 cases with disease activity in patients with uveitis, according to different classification to summarize and record ESR and other inflammatory markers, the condition score according to the scoring criteria. 2 three-color immunofluorescence staining, flow cytometry analysis, detection of uveitis patients and control peripheral blood cell surface CD4, CD25, CTLA-4 expression in CD4 expression analysis of CD4 CD25hig proportion their CD4 CD25high CTLA-4 cells. Moreover, with the different types of patients with different disease severity correlation analysis. Intracellular immunofluorescence staining, flow cytometry method to detect of intracellular CD4 cell factor IFN-γ, TNF-α and IL-10 expression analysis in between, with the severity of the disease and the cell surface the correlation of the expression of CD4 CD25high. By ELISA method, the detection of peripheral blood mononuclear cells in patients with uveitis of IFN-γ in the culture supernatant of TNF-α and IL-10 expression, analysis of the correlation with the severity of the disease and its cell surface expression of CD4 CD25high. Results: 1. Peripheral blood of patients with uveitis compared to the percentage of CD4 CD25high T cells with normal healthy controls (8.56 ± 4.22% vs.5.72 ± 3.11%), significantly higher (P = 0.022), and with the patient's condition is serious significantly positive correlation (P = 0.007). Expression between patients with different types of uveitis was no significant difference (P gt; 0.05). In addition, CD4 CD25highCTLA4 T cells in the peripheral blood of patients with uveitis compared to normal controls was significantly higher (P = 0.012). Positive percentage of IFN-γ expression in CD4 T cells in the peripheral blood of patients with uveitis 7.02 ± 4.86%, compared with normal healthy controls (4.19 ± 3.38%) was significantly higher (P = 0.026). The percentage of positive expression in CD4 T cells in the peripheral blood of patients with uveitis of TNF-α cells to 10.22 ± 5.61%, compared with normal healthy controls (6.75 ± 4.18%) was significantly higher (P = 0.023). IL-10 expression in CD4 cells of patients with uveitis proportion is slightly higher than that of normal healthy controls, but no significant difference in the statistics. These three cellular cytokine expression in CD4 cells and the severity of the patient's condition were significantly related to sex (P lt; 0.05) between significant correlation (P lt; 0.05). Also found that TNF-α, IL-10 expression in peripheral blood CD4 CD25high showed significant correlation (P lt; 0.05). 4. ELISA method found in patients with uveitis peripheral blood lymphocytes secrete IFN-γ in the supernatant of TNF-α expression and normal healthy controls were significantly higher (P lt; 0.05), and obvious correlation with disease (P lt; 0.05). IL-10 in patients with uveitis peripheral blood mononuclear cell culture supernatant expression levels compared with healthy controls slightly higher, but no significant differences (P gt; 0.05). Conclusion: It was found that: the peripheral blood of patients with uveitis the CD4 CD25high ratio was significantly higher than the healthy control group closely associated with Treg cells CTLA-4 was also found expression in CD4 CD25high Treg cells of patients with uveitis high preliminary prompted CD4 CD25 Treg may play an important role in the pathogenesis of uveitis, and is closely related with the disease activity. 2. Establish intracellular intracellular factor expression detection system, confirmed in the peripheral blood of patients with uveitis CD4 cell cytokines IFN-γ, TNF-α expression elevated compared with normal healthy controls, possibly as an important proinflammatory cytokines involved in uveal inflammation disease. The uveitis in peripheral blood of patients with CD4 cell expression of TNF-α and IL-10 and CD4 CD25 regulatory T cells express a certain correlation preliminary prompted these cytokines and CD4 CD25high relationship may be affected by regulation. Establishment of the experimental system for further in-depth study of uveitis CD4 CD25 regulatory T cells specific mechanism to provide a good protection, the results further reveal the immunological pathogenesis of uveitis, and further Immunology of uveitis treatment provides a clue.

Preliminary Study on the Expression and Role of CD4~+ CD25~+ Regulatory T Cells in Uveitis

Abstract

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