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: 6741484
• 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/6741484
• 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）：本研究的长期目标是 增进对疟疾与宿主相互作用机制的了解 免疫系统和 Epstein-Barr 病毒 (EBV) 促进发育 地方性伯基特淋巴瘤（eBL）。疟疾大流行之间的关联 儿童时期的 EBV 感染和 eBL 在非洲已很成熟。 EBV特异性 HLA I 类限制性 CD8+ 细胞毒性 T 淋巴细胞反应限制 感染EBV的B细胞增殖。这些和其他发现表明 疟疾抑制 EBV 特异性免疫，从而促进 eBL 的出现。疟疾改变 EBV 免疫力的机制 其在 eBL 发病机制中的作用尚不清楚。 该指导培训奖建立在 Case Western 之间的合作基础上 储备大学和肯尼亚医学研究所。提案 将检验以下假设：EBV 特异性 T 细胞免疫不会因 疟疾暴露本身，但病毒免疫是短暂而深刻的 在急性疟疾发病期间受到抑制，从而提供 潜伏感染的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 细胞免疫将受到影响。 自从抑制了 eBL 的这种先前发展以来，完好无损。具体的 目标将测试以下假设： 目标 1：EBV 特异性 T 细胞 IFN-y 和 IL-I0 反应随着时间的推移是稳定的，并且不受模式的影响 疟疾在健康儿童群体中的传播。目标 2：EBV 特异性 IFN-γ T 细胞反应被短暂抑制，而 IL-10 T 细胞反应被暂时抑制 是在疟疾发病期间诱发的。目标 3：EBV 特异性 T 细胞 eBL 儿童的 IFN-γ 和 IL-I0 反应是定性的和 数量上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 疫苗试验将在患有这种淋巴瘤的人群中进行 高患病率。