Immunologic Studies of Endemic Burkitt's Lymphoma

地方性伯基特淋巴瘤的免疫学研究

• 批准号: 6890001
• 负责人: ANN M MOORMANN
• 金额: $ 12.35万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6890001
• 关键词: African; B lymphocyte; Burkitt' s lymphoma; Epstein Barr virus; Plasmodium falciparum; T lymphocyte; cellular immunity; children; clinical research; comorbidity; host organism interaction; human subject; interferon gamma; interleukin 10; leukocyte activation /transformation; malaria; microorganism immunology; pathologic process; patient oriented research

DESCRIPTION (provided by applicant): The long-term goal of this research is to advance knowledge of the mechanism by which malaria interacts with the host immune system and Epstein-Barr virus (EBV) to promote the development of endemic Burkitt?s lymphoma (eBL). An association between holoendemic malaria, EBV infection and eBL during childhood is well established in Africa. EBV -specific HLA class I-restricted CD8+ cytotoxic T lymphocyte responses limit proliferation of B cells infected with EBV. These and other findings suggest that malaria suppresses EBV- specific immunity and thereby promotes the emergence of eBL. The mechanisms by which malaria alters immunity to EBV and its role in the pathogenesis of eBL are poorly understood. This mentored-training award builds upon collaborations between Case Western Reserve University and the Kenya Medical Research Institute. The proposal will test the hypothesize that EBV -specific T cell immunity is not altered by malaria exposure per se but that viral immunity is transiently and profoundly suppressed during episodes of acute malaria morbidity, thereby providing the opportunity for latently infected B cells to undergo malignant transformation. Thus, in children presenting with eBL, EBV -specific T cell immunity will be intact since suppression of such preceded development of eBL. The specific aims will test the following hypotheses: Aim 1: EBV-specific T cell IFN-y and IL-I0 responses are stable over time and not influenced by the pattern of malaria transmission in a population of healthy children. Aim 2: EBV-specific IFN-y T cell responses are transiently suppressed while IL-I0 T cell responses are induced during an attack of malaria morbidity. Aim 3: EBV-specific T cell IFN-y and IL-I0 responses in children with eBL are qualitatively and quantitatively similar to that of age-matched controls. Characterization of EBV-driven T cell responses associated with malaria will have implications for EBV vaccine trials to be conducted in populations where this lymphoma has a high prevalence.

描述（由申请人提供）：这项研究的长期目标是 促进了解疟疾与宿主相互作用的机制的知识 免疫系统和爱泼斯坦 - 巴尔病毒（EBV） 伯基特特有的淋巴瘤（EBL）。全神贯疟疾之间的关联， 童年时期的EBV感染和EBL在非洲已建立。 EBV特定 HLA I限制的CD8+细胞毒性T淋巴细胞反应极限 感染EBV的B细胞的增殖。这些发现和其他发现建议 疟疾抑制了特定EBV的免疫力，从而促进了 EBL的出现。疟疾改变对EBV的免疫力的机制和 它在EBL的发病机理中的作用知之甚少。 这个受过指导的培训奖是基于案例西方之间的合作 预备大学和肯尼亚医学研究所。提案 将测试假设的EBV特异性T细胞免疫不会改变 疟疾本身的暴露本身，但这种病毒免疫是短暂和深刻的 在急性疟疾发病的发作中被抑制，从而提供 潜在感染的B细胞发生恶性转化的机会。 因此，在出现EBL的儿童中，EBV特异性T细胞免疫将是 完整是因为抑制了EBL的这种先前的发展。具体 AIMS将检验以下假设：AIM 1：EBV特异性T细胞IFN-Y和 IL-I0响应随着时间的流逝而稳定，不受模式的影响 健康儿童人群中的疟疾传播。 AIM 2：EBV特异性 IFN-Y T细胞响应在IL-I0 T细胞响应时会瞬时抑制 在疟疾发病率发作期间被诱导。 AIM 3：EBV特异性T细胞 EBL儿童的IFN-Y和IL-I0反应在质量上是 定量与年龄匹配的对照相似。表征 与疟疾相关的EBV驱动的T细胞反应将对 EBV疫苗试验将在该淋巴瘤有A的种群中进行 高患病率。