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

1. 通过测定体外产生ifn - γ和IL-10的动力学，研究了C57BL/6 （B6）小鼠在致死性（PyL）或非致死性（PyNL）血期约氏疟原虫17X感染过程中T辅助细胞亚群的诱导。在这两种感染中，脾细胞在感染早期的培养中释放ifn - γ。相比之下，PyL感染小鼠的脾细胞产生高水平的IL-10，这与ifn - γ的产生同时发生，尽管PyNL感染小鼠的脾细胞不能产生IL-10。CD4^+ T细胞和非T细胞是PyL感染中IL-10的来源。用抗ifn - γ单抗治疗小鼠加重了高寄生虫血症的感染，所有小鼠在较正常大鼠Ig治疗后死亡。相反，当小鼠注射抗il -10单抗时，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。感染小鼠的脾脏细胞（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，这表明当时脾脏巨噬细胞群被激活。inf - γ似乎参与了活化，因为抗inf - γ治疗的脾脏细胞以剂量依赖的方式减少了亚硝酸盐的产生。相比之下，用抗il -10处理感染小鼠的脾脏细胞可促进亚硝酸盐的产生。这些结果表明，在PyL感染时，辅助性T淋巴细胞的Th1和Th2亚群都被激活，而在PyNL感染时，只有Th1亚群被激活。此外，这些数据表明，尽管ifn - γ是疟疾免疫的关键分子，但在感染早期强烈的IL-10应答可能通过抑制巨噬细胞功能在疟疾感染的恶化中发挥重要作用。

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.