T cell apoptosis in primate model for severe human malaria.

将猴疟原虫（CDC株）的无性期疟原虫（Plasmodium coatneyi， CDC株）静脉接种于对该疟原虫感染易感程度不同的两种猕猴——日本猕猴（Macaca fuscata）和食蟹猕猴（M. fascicularis）。感染革内疟原虫的日本猕猴表现出与人类重症疟疾相似的严重临床表现，而感染食蟹猕猴除贫血外无其他严重疾病表现，最终痊愈。在感染的日本猕猴中，外周血CD4^+和CD8^+ T细胞群明显减少，外周血单核细胞染色体DNA片段化，提示凋亡细胞死亡是T淋巴细胞减少的原因。此外，感染的日本猕猴在死亡后血清中可溶性Fas配体水平逐渐升高至显著的高水平。另一方面，感染的食蟹猴既没有T淋巴细胞减少症，也没有可溶性Fas配体水平升高。这些发现表明，受试的两种猕猴之间的免疫应答差异解释了感染同一疟原虫分离物后的不同结果，特别是由于fas衍生的细胞凋亡引起的深度T淋巴细胞减少症在受感染的日本猕猴的疟疾致命过程中发挥了作用。

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.