Dendritic cells (DCs) can induce both tolergenic as well as effective immune responses in the lung. Pulmonary DCs producing interleukin (IL)-10 mediated tolerance induced by respiratory exposure to antigen. IL-10 is an important immunosuppressive cytokine, which inhibits maturation and function of DC. To assess whether IL-10 producing DCs can exert the tolergenic effect through the differentiation of regulatory T cells, bone marrow derived DCs were genetically modified by IL-10 expressing adenovirus. IL-10 gene modified DCs (Ad-IL-10-DC) displayed a characteristic phenotype of immature DCs. Here we showed that in vitro repetitive stimulation of naïve DO11·10 CD4+ T cells with Ad-IL-10-DCs resulted in a development of IL-10 producing T-cell regulatory cells. These T cells could not proliferate well but also lost their ability to produce interferon-γ upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naïve CD4+ T cells in a dose-dependent manner. Our findings demonstrated that IL-10 producing DCs had the potential to induce the differentiation of Tr1-like cells and suggested their therapeutic use. 相似文献
PURPOSE: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of viable vascular endothelial cells in tumors, possibly in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a monoclonal antibody directed against anionic phospholipids might exert antitumor effects by causing vascular damage in tumors. EXPERIMENTAL DESIGN: A new mouse immunoglobulin G3 monoclonal antibody, 3G4, was raised that binds anionic phospholipids in the presence of serum or beta2-glycoprotein I. The antibody was tested for its ability to localize to tumor vessels and exert antitumor effects in mice. RESULTS: 3G4 recognized anionic phospholipids on the external membrane of H(2)O(2)-treated endothelial cells and in vitro. It localized specifically to tumor vascular endothelium and to necrotic tumor cells after injection into severe combined immunodeficient mice bearing orthotopic MDA-MB-435 tumors. Treatment with 3G4 retarded the growth of four different tumors in mice. It reduced the growth of established orthotopic MDA-MB-231 and MDA-MB-435 human breast tumors in mice by 75% and 65% respectively, large L540 human Hodgkin's tumors by 50%, and small syngeneic Meth A fibrosarcomas by 90%. Histologic examination revealed vascular damage, a reduction in vascular density, and a reduction in tumor plasma volume. Treatment with 3G4 induced the binding of monocytes to tumor endothelium and infiltration of macrophages into MDA-MB-435 and MDA-MB-231 tumors. No toxicity to the mice was observed. CONCLUSIONS: 3G4 localizes specifically to complexes of anionic phospholipids and serum proteins on the surface of vascular endothelial cells in tumors in mice. This results in damage to tumor vasculature and suppression of tumor growth. 相似文献
Aim: Returning to society plays an important role in improving the quality of life in maintenance hemodialysis (MHD) patients, and retention of employment is one of the core enablers. The study is to assess the employment status and to determine the variables for unemployment in Chinese MHD patients.
Methods: Prevalent MHD patients from four dialysis centers in Shanghai China were enrolled. We assessed patients’ employment status, current social functioning, hemodialysis modality, annual income and general health condition. Among current unemployed working-age patients, the reasons of quitting jobs and willingness of being reemployed were evaluated.
Results: A total of 231 patients were studied, among which 114 patients were unemployed 1 year before hemodialysis. Among 117 employed patients, 16 patients quitted jobs before dialysis inception, while 49 patients quitted jobs at the initiation of HD, and 26 patients followed after a few months’ HD. The main reasons for ceasing employment were physical insufficiency, conflict between dialysis and work schedules, lack of support from employers and resistance from family members. Among the 166 patients who were in their working age, 26 patients were employed. The unemployed patients had the characters of elder age, lower education level, higher annual family income, higher female ratio, lower blood flow, lower physical functioning, and social functioning and lower frequency of weekend hemodialysis and HDF/HF. Among the 140 unemployed patients, only 47 patients had the willingness of being reemployed. Their unemployment status was positively associated with elder age ((OR) 3.13, 95% CI, 1.08–9.1), lower education level ((OR) 1.97, 95% CI, 1.05–5.92), and higher family income ((OR) 7.75, 95% CI, 2.49–24.14).
Conclusion: Ratio of employment and willingness of being reemployed was low in MHD working-age patients. Lack of social and family’s support also hampered patient’s returning to society except for the HD treatment quality. 相似文献