Immunologic Studies of Endemic Burkitt's Lymphoma

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EB病毒（EBV），以促进发展 地方性伯基特病s淋巴瘤（eBL）。全地方性疟疾， 在非洲，儿童期的EBV感染和eBL已得到很好的证实。EBV特异性 HLA I类限制性CD 8+细胞毒性T淋巴细胞应答限值 EBV感染的B细胞增殖。这些和其他发现表明， 疟疾抑制EB病毒特异性免疫，从而促进 EBL的出现。疟疾改变对EBV免疫的机制， 其在eBL发病机制中的作用知之甚少。 这个指导培训奖建立在凯斯西方之间的合作基础上， 储备大学和肯尼亚医学研究所。该提案 将检验EBV特异性T细胞免疫性不被 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细胞有机会发生恶性转化。 因此，在患有eBL的儿童中，EBV特异性T细胞免疫将被抑制。 因为抑制了这种早期的eBL发展。具体 目的1：EBV特异性T细胞IFN-γ和IFN-γ受体， IL-10应答随时间推移是稳定的，并且不受IL-10表达模式的影响。 疟疾在健康儿童群体中的传播。目的2：EBV特异性 IFN-γ T细胞应答被瞬时抑制，而IL-10 T细胞应答 是在疟疾发病期间诱发的。目的3：EBV特异性T细胞 IFN-γ和IL-10的反应在儿童与eBL是定性和 与年龄匹配的对照组在数量上相似。表征 与疟疾相关的EBV驱动的T细胞应答将对以下方面产生影响： EB病毒疫苗试验将在这种淋巴瘤有以下症状的人群中进行： 高流行率。

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.