T cell apoptosis in primate model for severe human malaria.

将猴疟原虫Coatneyi（CDC株）的无性阶段静脉接种到对该寄生虫感染具有不同易感性的两种猕猴中，即日本猕猴（Macaca fuscata）和食蟹猴（M. fascicularis）。感染Coatneyi疟原虫的日本猕猴出现了与严重的人类疟疾相似的严重临床表现，而感染的食蟹猴除了贫血外没有表现出严重的疾病表现，并最终从感染中恢复。在感染的日本猕猴中，外周血CD4^+和CD8^+ T细胞群显著减少，并且在感染的终末期检测到外周血单个核细胞中染色体DNA的断裂，这表明凋亡性细胞死亡是T淋巴细胞减少的原因。此外，可溶性Fas配体水平在感染的日本猕猴血清中逐渐增加到一个显着的高水平时，他们成为濒死。另一方面，没有感染的食蟹猴表现出T淋巴细胞减少或可溶性Fas配体水平升高。这些研究结果表明，两种猕猴之间的免疫反应的差异测试占对比的结果感染后，与相同的分离的疟疾寄生虫，特别是一个深刻的T淋巴细胞减少症由于Fas衍生的细胞凋亡中发挥了作用的致命过程中的疟疾感染的日本猕猴。

The asexual stage of the simian malaria parasite, Plasmodium coatneyi (CDC strain), was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, Japanese macaques (Macaca fuscata) and cynomolgus macaques (M. fascicularis). The Japanese macaques infected with P. coatneyi developed severe clinical manifestations similar to those of severe human malaria, while the infected cynomolgus macaques, exhibited no severe manifestation of disease except anemia, and finally recovered from the infection. In the infected Japanese macaques, peripheral CD4^+ and CD8^+ T-cell populations were markedly decreased and fragmentation of chromosomal DNA in peripheral blood mononuclear cells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible for the T lymphocytopenia. Furthermore, soluble Fas ligand level in serum of the infected Japanese macaques increased gradually to a markedly high level when they became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or the elevation of soluble Fas ligand level. These findings suggest that differences in immune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial parasite, and in particular that a profound T lymphocytopenia due to Fas-derived apoptosis played a role in the fatal course of malaria in the infected Japanese macaques.