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Cutting Edge: Attrition of Plasmodium-Specific Memory CD8 T Cells Results in Decreased Protection That Is Rescued by Booster Immunization

机译:尖端:疟原虫特异性记忆CD8 T细胞的磨损导致增强保护被递减免疫所挽救

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Sterile protection against infection with Plasmodium sporozoites requires high numbers of memory CD8 T cells. However, infections with unrelated pathogens, as may occur in areas endemic to malaria, can dramatically decrease pre-existing memory CD8 T cells. It remains unknown whether unrelated infections will compromise numbers of Plasmodium -specific memory CD8 T cells and thus limit the duration of antimalarial immunity generated by subunit vaccination. We show that P . berghei circumsporozoite-specific memory CD8 T cells underwent significant attrition in numbers in mice subjected to unrelated infections. Attrition was associated with preferential loss of effector memory CD8 T cells and reduced immunity to P. berghei sporozoite challenge. However, and of relevance to deployment of Plasmodium vaccines in areas endemic to malaria, attrition of memory CD8 T cells was reversed by booster immunization, which restored protection. These data suggest that regular booster immunizations may be required to sustain protective vaccine-induced Plasmodium -specific memory CD8 T cells in the face of attrition caused by unrelated infections.
机译:防止疟原虫子孢子感染的无菌保护需要大量的记忆CD8 T细胞。但是,与无关病原体的感染(可能发生在疟疾流行地区)可能会大大减少先前存在的记忆CD8 T细胞。无关的感染是否会损害疟原虫特异性记忆CD8 T细胞的数量,从而限制亚单位疫苗接种产生的抗疟疾免疫力的持续时间,仍然是未知的。我们证明P。在遭受无关感染的小鼠中,伯氏疟原虫环子孢子特异性记忆CD8 T细胞的数量显着减少。损耗与效应记忆CD8 T细胞的优先丢失和对伯氏疟原虫子孢子攻击的免疫力降低有关。但是,与在疟疾流行地区部署疟原虫疫苗有关,通过加强免疫可以逆转记忆CD8 T细胞的消耗,从而恢复保护作用。这些数据表明,面对由无关感染引起的减员,可能需要定期加强免疫,以维持保护性疫苗诱导的疟原虫特异性记忆CD8 T细胞。

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