T cell apoptosis in primate model for severe human malaria.

严重人类疟疾灵长类动物模型中 T 细胞凋亡。

• 批准号: 12670239
• 负责人: KAWAI Satoru
• 金额: $ 1.73万
• 依托单位: Dokkyo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670239/
• 关键词: Severe malaria; primate model; Japanese macaque; T cell; apoptosis; TUNEL staining; soluble Fas ligand; MMPI; Fas抗原

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.

将处于无性阶段的猿猴疟原虫科特尼疟原虫（CDC 株）静脉接种到对这种寄生虫感染具有不同敏感性的两种猕猴体内，即日本猕猴（Macaca fuscata）和食蟹猴（M. fascicularis）。感染科氏疟原虫的日本猕猴出现了与严重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，最终从感染中康复。在受感染的日本猕猴中，在感染末期，外周血CD4^+和CD8^+ T细胞数量明显减少，并且检测到外周血单核细胞中染色体DNA断裂，表明细胞凋亡是T细胞死亡的原因。淋巴细胞减少症。此外，受感染的日本猕猴血清中可溶性Fas配体水平在濒临死亡时逐渐升高至显着高水平。另一方面，受感染的食蟹猴均未表现出 T 淋巴细胞减少或可溶性 Fas 配体水平升高。这些发现表明，所测试的两种猕猴之间免疫反应的差异导致了感染同一疟疾寄生虫分离株后的截然不同的结果，特别是 Fas 衍生的细胞凋亡导致的严重 T 淋巴细胞减少在致命性中发挥了作用。受感染的日本猕猴的疟疾病程。

项目成果

Kawazu S., Tsuji N., Hatabu T., Kawai S., Matsumoto Y., Kano S.: "Molecular cloning and characterization of a peroxiredoxin from the human malaria parasite Plasmodium falciparum"Mol. Biochem. Parasitol. 109. 165-169 (2000)

Kawazu S.、Tsuji N.、Hatabu T.、Kawai S.、Matsumoto Y.、Kano S.：“来自人类疟疾寄生虫恶性疟原虫的过氧化还原蛋白的分子克隆和表征”Mol。

Kawazu S.,Tsuji N.,Hatabu T.,Kawai S.,Matsumoto Y.,Kano S.: "Molecular cloning and characterization of a peroxiredoxin from the human malaria parasite Plasmodium falciparum."Mol.Bio.Parasitol.. 109. 165-169 (2000)

Kawazu S.、Tsuji N.、Hatabu T.、Kawai S.、Matsumoto Y.、Kano S.：“来自人类疟原虫恶性疟原虫的过氧化还原蛋白的分子克隆和表征。”Mol.Bio.Parasitol.. 109。

Kawai S.: "Role of promate models in the study of human falciparum"J. Anim. Protozooses. 16. 54-59 (2001)

Kawai S.：“原动物模型在人类恶性疟原虫研究中的作用”J。

Matsumoto J., Kawai S, Terao K., Kirinoki M., Yasutomi Y., Aikawa M., Matsuda H.: "Malaria infection induces rapid elevation of the soluble Fas ligand level in serum and subsequent T lymphocytopenia : possible factors responsible for the differences in su

Matsumoto J.、Kawai S、Terao K.、Kirinoki M.、Yasutomi Y.、Aikawa M.、Matsuda H.：“疟疾感染导致血清中可溶性 Fas 配体水平快速升高，并随后导致 T 淋巴细胞减少：可能是导致

川合 覚: "熱帯熱マラリア研究におけるサル類の役割"動物の原虫病. 16. 54-59 (2001)

Satoru Kawai：“猴子在恶性疟疾研究中的作用”动物原生动物疾病。 16. 54-59 (2001)