Immunologic Studies of Endemic Burkitt's Lymphoma

描述(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EB病毒(EBV)促进肿瘤的发展 地方性Burkitt？S淋巴瘤。全流行疟疾之间的联系， 儿童时期的EBV感染和EBL在非洲很普遍。EBV特异性 人类白细胞抗原I类限制的CD8+细胞毒性T淋巴细胞反应极限 EB病毒感染的B细胞的增殖。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。疟疾改变对EBV和EBV免疫的机制 目前对其在EBL发病机制中的作用知之甚少。 这一指导培训奖建立在凯斯·韦斯特 后备大学和肯尼亚医学研究所。这项建议 将检验EBV特异性T细胞免疫不被改变的假设 疟疾暴露本身，但这种病毒免疫力是短暂和深刻的 在急性疟疾发病期间被抑制，从而提供 潜伏感染的B细胞发生恶变的机会。 因此，在出现EBL的儿童中，EBV特异性T细胞免疫将是 由于在EBL的发展之前抑制了这种情况，所以完好无损。具体的 AIMS将检验以下假设：AIMS 1：EBV特异性T细胞干扰素-γ和 IL-I0反应随着时间的推移是稳定的，不受 疟疾在健康儿童群体中的传播。目标2：特定于EB病毒 干扰素-γT细胞反应被一过性抑制，而白介素10 T细胞反应被暂时抑制 是在疟疾发病率发作期间诱发的。目标3：EBV特异性T细胞 EBL患儿的干扰素-γ和白介素10反应定性和定量 在数量上与年龄匹配的对照组相似。特征描述 与疟疾相关的EBV驱动的T细胞反应将对 EBV疫苗试验将在这种淋巴瘤患者中进行 患病率很高。

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.