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

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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.