The induction and persistence of T cell IFN-γ responses after vaccination or natural exposure is suppressed by Plasmodium falciparum
The induction and persistence of T cell IFN-γ responses after vaccination or natural exposure is suppressed by Plasmodium falciparum
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DOI：
10.4049/jimmunol.179.6.4193
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
Hill, Adrian V. S.
中科院分区：
文献类型：
--
作者：
Bejon, Philip;Mwacharo, Jedidah;Hill, Adrian V. S.
流行病学观察表明，T细胞免疫可能在疟疾流行地区受到抑制。体外研究、动物模型和有限的人类数据将免疫抑制与疟疾、营养不良和其他寄生虫感染联系起来。但是，目前尚无资料确定疟疾引起的免疫抑制是否具有长期显著性，或将其与疟疾流行区其他因素进行比较的相关数据，以衡量疟疾、其他寄生虫病、营养状况、年龄等因素的影响。和位置上的收购和寿命的IFN-γ反应在肯尼亚的儿童。我们研究了这些因素在两个队列的1至6岁的儿童在疟疾流行区。在一个队列中通过疫苗接种诱导T细胞应答，并且在第二队列中作为自然暴露的结果获得T细胞应答。在一年的时间内进行的系列ELISPOT测定测量响应于疟疾Ag血小板反应蛋白相关粘附蛋白的IFN-γ产生的诱导和动力学。将两个队列中的诱导应答和接种队列中的应答持续时间与潜在解释变量拟合。在两个队列中，寄生虫血症与产生IFN-γ的T细胞减少（15-25%）前瞻性相关，寄生虫血症和发热性疟疾发作分别与T细胞应答增加19%和31%相关。疟疾可能会降低疫苗接种（如卡介苗和试验性T细胞诱导疫苗）的效力，并可能延迟自然暴露于疟疾和其他病原体后获得免疫力。
Epidemiological observations suggest that T cell immunity may be suppressed in malaria-endemic areas. In vitro studies, animal models, and limited data in humans link imnmnosuppression with malaria, malnutrition, and other parasitic infections. However, there are no data to determine whether malaria-induced immunosuppression is significant in the long-term, or relative data comparing it with other factors in malaria-endemic areas, so as to measure the impact of malaria, other parasitic disease, nutritional status, age. and location on the acquisition and longevity of IFN-gamma responses in children in Kenya. We studied these factors in two cohorts of 1- to 6-year-old children in a malaria-endemic area. T cell responses were induced by vaccination in one cohort, and acquired as a result of natural exposure in a second cohort. Serial ELISPOT assays conducted over a I-year period measured the induction and kinetics of IFN-gamma production in response to the malaria Ag thrombospondin-related adhesion protein. Induced responses in both cohorts and the longevity of response in the vaccinated cohort were fitted to potential explanatory variables. Parasitemia was prospectively associated with reduced IFN-gamma-producing T cells in both cohorts (by 15-25%), and both parasitemia and episodes of febrile malaria were associated with 19 and 31% greater attrition of T cell responses, respectively. Malaria may reduce the efficacy vaccinations such as bacillus Calmette-Guerin and investigational T cell-inducing vaccines, and may delay the acquisition of immunity following natural exposure to malaria and other pathogens.