S MANSONI HEPATOSPLENISM AND HLA AND T CELL RESPONSES

S MANSONI 肝脾功能与 HLA 和 T 细胞反应

• 批准号: 6474051
• 负责人: MITERMAYER REIS
• 金额: $ 25.46万
• 依托单位: FEDERAL UNIVERSITY OF BAHIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-15 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6474051
• 关键词: MHC class II antigen; Schistosoma mansoni; T lymphocyte; alleles; antiantibody; antigen antibody reaction; biomarker; cell cycle; cellular immunity; clinical research; cytokine; enzyme linked immunosorbent assay; flow cytometry; human subject; immunoregulation; longitudinal human study; medical complication; parasitic liver disorder; polymerase chain reaction; protozoal antigen; schistosomiasis; spleen disorder

Hepatosplenic disease can be a life threatening complication of schistosomiasis. In this regard, we have recently demonstrated the strong association of HLA class II allele DQbeta*0201 with the development of hepatosplenic disease in Brazilian patients. This allele is associated with other diseases with defects in immune regulation, celiac disease and insulin dependent diabetes. We hypothesize that this MHC Class 2 allele influences the priming of T cells leading to a response distinct from individuals with other DQ haplotypcs. Further, analysis of HLA Class 2 alleles and patients immune responses showed a strong association of alleles DQbeta1*0501, DQalpha1*0101 and DR1 with lowered or no response to soluble egg antigens as compared to the total patient population. We propose to compare the in vitro priming response of peripheral blood mononuclear cells (PBMC) to schistosome antigens of individuals carrying these alleles to individuals carrying DQ and DR alleles where no statistical association was shown with disease. The response to schistosome antigens would then be compared to the response from the same individuals to third party antigen such as PPD. We will measure the in vitro priming (IVP) cytokine profiles/proliferation of naive PBMC to schistosome antigens, and then correlate these results with HLA Class II haplotype. Then we will determine if these responses are representative of in vitro responses of HLA Class II matched PBMC from patients prior to, or after development of hepatosplenic disease. We will see if HLA Class II haplotype correlate with expression of MHC class II and co-stimulatory molecules on PBMC after IVP with Schistosome antigens. We will determine whether the IVP response to schistosome antigens can be altered by treatment with exogenous cytokines or anti-cytokine antibodies, and whether the ability to be altered correlates with HLA Class II haplotype. These studies should provide significant new data on the influence of HLA Class II alleles on development and control of cellular immune responses to schistosome antigens and lead to predictive markers for resistance/susceptibility or the likelihood of developing disease.

肝嗜性疾病可能是威胁生命的并发症 血吸虫病。 在这方面，我们最近证明了强者 HLA II类等位基因DQBETA*0201的协会与发展 巴西患者的肝肾上腺病。 这个等位基因是关联的 与免疫调节，乳糜泻和 胰岛素依赖性糖尿病。 我们假设这个MHC 2类等位基因 影响T细胞的启动，导致与 患有其他DQ HaplotyPCS的人。 此外，对HLA 2类的分析 等位基因和患者免疫反应显示 等位基因dqbeta1*0501，dqalpha1*0101和dr1，降低或没有响应 与总患者人群相比，可溶性卵抗原。 我们 建议比较外周血的体外启动反应 单核细胞（PBMC）到携带的个体的血吸虫抗原 这些等位基因携带DQ和DR等位基因的个人 统计关联显示了疾病。 对 然后将血吸虫抗原与同一反应进行比较 个人到第三方抗原，例如PPD。 我们将测量体外启动（IVP）细胞因子谱/增殖 幼稚的PBMC与螺杆菌抗原，然后将这些结果相关联 与HLA II类单倍型。 然后，我们将确定这些反应是否 代表了HLA II类体外反应与来自 患者在发生肝脾疾病之前或发展后。 我们将 查看HLA II类单倍型是否与MHC II类表达相关 IVP之后，用烟素抗原在PBMC上的共刺激分子。 我们将确定IVP对螺杆菌抗原的反应是否可以 通过外源细胞因子或抗环胞因子抗体的治疗改变， 以及是否改变的能力与HLA II类相关 单倍型。 这些研究应提供有关HLA影响的重要新数据 关于细胞免疫反应的开发和控制的II类等位基因 到棘小体抗原，并导致预测标记 抗药性/敏感性或发展疾病的可能性。