Data_Sheet_1_Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria.PDF

In Plasmodium falciparum malaria, CD8+ T cells play a double-edged role. Liver-stage specific CD8+ T cells can confer protection, as has been shown in several vaccine studies. Blood-stage specific CD8+ T cells, on the other hand, contribute to the development of cerebral malaria in murine models of malaria. The role of CD8+ T cells in humans during the blood-stage of P. falciparum remains unclear. As part of a cross-sectional malaria study in Ghana, granzyme B levels and CD8+ T cells phenotypes were compared in the peripheral blood of children with complicated malaria, uncomplicated malaria, afebrile but asymptomatically infected children and non-infected children. Granzyme B levels in the plasma were significantly higher in children with febrile malaria than in afebrile children. CD8+ T cells were the main T cell subset expressing granzyme B. The proportion of granzyme B+ CD8+ T cells was significantly higher in children with complicated malaria than in uncomplicated malaria, whereas the activation marker CD38 on CD8+ T cells showed similar expression levels. This suggests a pathogenic role of cytotoxic CD8+ T cells in the development of malaria complications in humans.

在恶性疟疾中，CD8+ T细胞扮演着双刃剑的角色。针对肝脏期特定CD8+ T细胞的研究表明，它们能够提供保护作用，这在多项疫苗研究中已得到证实。然而，在恶性疟疾的血液期，特定CD8+ T细胞在鼠类疟疾模型中会促进脑型疟疾的发展。关于人类在恶性疟疾血液期CD8+ T细胞的作用仍处于模糊状态。作为加纳横断面疟疾研究的一部分，研究人员对比了复杂疟疾、非复杂疟疾儿童、无症状但感染的非发热儿童以及未感染儿童的周围血液中的颗粒酶B水平及CD8+ T细胞表型。血浆中的颗粒酶B水平在发热疟疾儿童中显著高于非发热儿童。CD8+ T细胞是主要表达颗粒酶B的T细胞亚群。在复杂疟疾儿童中，颗粒酶B+ CD8+ T细胞的比率显著高于非复杂疟疾儿童，而CD8+ T细胞上的活化标志物CD38的表达水平则显示出相似的趋势。这表明，细胞毒性CD8+ T细胞在人类疟疾并发症的发展中可能起着致病作用。