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The role of T-lymphocytes and cytokines in immunity to malaria.

T 淋巴细胞和细胞因子在疟疾免疫中的作用。

基本信息

批准号：
05670237
负责人：
KOBAYASHI Fumie
金额：
$ 1.47万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

1. The induction of T helper cell subsets during the course of lethal (PyL) or nonlethal (PyNL) blood-stage Plasmodium yoelii 17X infection was investigated using C57BL/6 (B6) mice by determining the kinetics of in vitro production of IFN-gamma and IL-10. In both infections, spleen cells released IFN-gamma in culture in the early stage of infections. In contrast, spleen cells from mice infected with PyL produced high levels of IL-10, which was concomitant with the production of IFN-gamma, although spleen cells from mice infected with PyNL failed to produce IL-10. CD4^+ T cells as well as non T cells were the source of IL-10 in PyL infection.2. Treatment of mice with anti-IFN-gamma mAb exacerbated infection with high parasitemia and all mice died after an ealier period than those treated with normal rat Ig. On the contrary, when mice were injected with anti-IL-10 mAb, 60% of mice showed moderate levels of parasitemia and ultimately recovered from the infection.3. Spleen cells of infected mice (day 6) produced a significant amount of nitrite while uninfected control mice did not, suggesting that the splenic macrophage population was activated at the time. INF-gamma appeared to be involved in the activation becouse anti-INF-gamma treatment of the spleen cells decreased the nitrite production in a dose-dependent fasion. In contrast, treatment of spleen cells of infected mice with anti-IL-10 enhanced the nitrite production.Those results demonstrate that both Th1 and Th2 subsets of T helper lymphocytes are activated during PyL infection, while only Th1 subset of them is activated in PyNL infection. In addition, these data suggest that a strong IL-10 response in the early stage of infection may play an important role in exacerbation of malaria infections possibly by inhibiting macrophage functio, though IFN-gamma is a key molecule in immunity to malaria.

1.通过测定IFN-γ和IL-10的体外产生动力学，使用C57 BL/6（B6）小鼠研究了在致死（PyL）或非致死（PyNL）血液期约氏疟原虫17 X感染过程中T辅助细胞亚群的诱导。在这两种感染中，脾细胞在感染的早期阶段在培养物中释放IFN-γ。相比之下，来自感染PyL的小鼠的脾细胞产生高水平的IL-10，其伴随IFN-γ的产生，尽管来自感染PyNL的小鼠的脾细胞不能产生IL-10。PyL感染时，CD 4 ^+ T细胞和非T细胞是IL-10的来源.用抗IFN-γ单抗治疗小鼠加重了感染并伴有高寄生虫血症，所有小鼠在较用正常大鼠IG治疗的小鼠更早的时间后死亡。相反，当小鼠注射抗IL-10 mAb时，60%的小鼠表现出中等水平的寄生虫血症并最终从感染中恢复。感染小鼠的脾细胞（第6天）产生了大量的亚硝酸盐，而未感染的对照小鼠则没有，这表明脾巨噬细胞群在当时被激活。INF-γ参与了亚硝酸盐的激活，因为抗INF-γ处理脾细胞以剂量依赖性方式减少亚硝酸盐的产生。这些结果表明，在PyL感染过程中，辅助性T淋巴细胞的Th 1和Th 2亚群均被激活，而在PyNL感染过程中，辅助性T淋巴细胞的Th 1亚群仅被激活。此外，这些数据表明，虽然IFN-γ是疟疾免疫的关键分子，但在感染的早期阶段强烈的IL-10应答可能通过抑制巨噬细胞功能而在疟疾感染的恶化中起重要作用。