In the Plasmodium berghei ANKA mouse model of malaria, accumulation of CD8⁺ T cells and infected RBCs in the brain promotes the development of experimental cerebral malaria (ECM). In this study, we used malaria-specific transgenic CD4⁺ and CD8⁺ T cells to track evolution of T cell immunity during the acute and memory phases of P. berghei ANKA infection. Using a combination of techniques, including intravital multiphoton and confocal microscopy and flow cytometric analysis, we showed that, shortly before onset of ECM, both CD4⁺ and CD8⁺ T cell populations exit the spleen and begin infiltrating the brain blood vessels. Although dominated by CD8⁺ T cells, a proportion of both T cell subsets enter the brain parenchyma, where they are largely associated with blood vessels. Intravital imaging shows these cells moving freely within the brain parenchyma. Near the onset of ECM, leakage of RBCs into areas of the brain can be seen, implicating severe damage. If mice are cured before ECM onset, brain infiltration by T cells still occurs, but ECM is prevented, allowing development of long-term resident memory T cell populations within the brain. This study shows that infiltration of malaria-specific T cells into the brain parenchyma is associated with cerebral immunopathology and the formation of brain-resident memory T cells. The consequences of these resident memory populations is unclear but raises concerns about pathology upon secondary infection.

在伯氏疟原虫ANKA 疟疾小鼠模型中，大脑中 CD8 ⁺ T 细胞和受感染红细胞的积累促进了实验性脑型疟疾 (ECM) 的发展。在这项研究中，我们使用疟疾特异性转基因 CD4 ⁺和 CD8 ⁺ T 细胞来跟踪伯氏疟原虫ANKA 感染的急性和记忆阶段 T 细胞免疫的进化。使用活体多光子和共聚焦显微镜以及流式细胞术分析等技术组合，我们发现，在 ECM 开始前不久，CD4 ⁺和 CD8 ⁺ T 细胞群都离开脾脏并开始浸润脑血管。虽然以CD8 ⁺为主T 细胞，两种 T 细胞亚群的一部分进入脑实质，在那里它们主要与血管相关。活体成像显示这些细胞在脑实质内自由移动。在 ECM 发作附近，可以看到 RBC 泄漏到大脑区域，这意味着严重的损伤。如果小鼠在 ECM 发病前被治愈，T 细胞的大脑浸润仍然会发生，但 ECM 被阻止，允许在大脑内形成长期驻留记忆 T 细胞群。这项研究表明，疟疾特异性 T 细胞浸润到脑实质与脑免疫病理学和脑驻留记忆 T 细胞的形成有关。这些常驻记忆群体的后果尚不清楚，但引起了对继发感染后病理学的担忧。