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。使用C57BL/6（B6）小鼠，通过确定IFN-Gamma和IL-10的动力学，使用C57BL/6（B6）小鼠研究了致死性（PYL）或非致死性（Pynl）血液阶段疟原虫17X感染的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都释放了IFN-gamma。相比之下，感染了塔的小鼠的脾细胞产生了高水平的IL-10，这与IFN-gamma的产生伴随着，尽管感染了Pynl的小鼠的脾细胞未能产生IL-10。 CD4^+ T细胞以及非T细胞是PYL感染中IL-10的来源。2。用抗寄生虫血症高的抗IFN-gamma mAb加剧感染的小鼠与正常大鼠Ig治疗的小鼠死亡。相反，当给小鼠注射抗IL-10 MAB时，有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。3。感染小鼠的脾细胞（第6天）产生了大量亚硝酸盐，而未感染的对照小鼠则没有，这表明当时激活了脾巨噬细胞群体。由于脾细胞的抗Inf-gamma治疗降低了剂量依赖性的伪造中的亚硝酸盐产生，因此INF-GammA似乎参与了激活。相反，用抗IL-10的感染小鼠的脾细胞的治疗增强了亚硝酸盐的产生。这些结果表明，T辅助淋巴细胞的Th1和Th2亚群在PYL感染过程中都被激活，而仅在Pynl感染中仅激活它们的Th1亚集。此外，这些数据表明，在感染的早期阶段，强烈的IL-10反应在加剧疟疾感染中可能通过抑制巨噬细胞功能而发挥重要作用，尽管IFN-GAMMA是对疟疾的免疫力的关键分子。