S MANSONI HEPATOSPLENISM AND HLA AND T CELL RESPONSES

肝脾疾病可能是危及生命的并发症， 血吸虫病 在这方面，我们最近表现出了强大的 HLA II类等位基因DQ β *0201与以下疾病的发生相关： 巴西患者的肝脾疾病。 该等位基因与 与免疫调节缺陷的其他疾病，乳糜泻， 胰岛素依赖型糖尿病 我们假设这个MHC 2类等位基因 影响T细胞的引发，导致不同于 其他DQ单倍型的个体。 此外，HLA Class 2的分析 等位基因和患者的免疫反应显示出强烈的关联， 等位基因DQ β 1 *0501、DQ α 1 *0101和DR 1，对 可溶性卵抗原与总患者群体相比。 我们 建议比较外周血的体外预激反应 单个核细胞（PBMC）与携带 这些等位基因携带DQ和DR等位基因的个体， 统计学显示与疾病相关。 应对 然后将抗原与来自相同抗原的反应进行比较。 第三方抗原，如PPD。 我们将测量体外引发（IVP）细胞因子谱/增殖 的幼稚PBMC的抗原，然后将这些结果 HLA II类单倍型 然后我们将确定这些反应是否 代表来自HLA-II类匹配的PBMC的体外应答， 患者之前，或之后发展的肝脾疾病。 我们将 看HLA II类单倍型是否与MHC II类表达相关 血吸虫抗原IVP后PBMC上的共刺激分子。 我们将确定IVP是否能对溶酶体抗原产生反应， 通过用外源性细胞因子或抗细胞因子抗体处理而改变， 以及被改变的能力是否与HLA II类相关 单倍型. 这些研究将提供重要的新数据，HLA的影响， II类等位基因对细胞免疫应答的发展和控制 来识别一些抗原， 抗性/易感性或发展疾病的可能性。

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.