Differential induction of helper T cell subsets during blood‐stage Plasmodium chabaudi AS infection in resistant and susceptible mice

SUMMARY The induction of T helper cell subsets during the course of non‐lethal or lethal blood‐stage Plasmodium chabaudi AS infection was investigated using inbred strains of mice which differ in the level of resistance to this intraerythrocytic parasite. Resistant C57B1/6 mice experience a non‐lethal course of infection characterized by moderate levels of both parasitaemia and anaemia and resolution of primary acute infection by 4 weeks, while susceptible A/J mice experience lethal infection with fulminant parasitaemia and severe anaemia. T helper subset function was assessed during infection by determining the kinetics of spleen cell production in vitro of the Th1‐derived cytokine, interferon‐gamma (IFN‐γ), and of the Th2‐dcrived cytokine, IL‐5, using sandwich ELISAs. Spleen cells from resistant C57B1/6 mice were found to produce high levels of IFN‐γ within 1 week of infection in response to both the mitogen concanavalin A (Con A) and malaria antigen. Furthermore, CD4 + T cells were found to be the source of I FN‐γ while both CD4 + and CD8 + T cells were found to produce IL‐5. Decreased IFN‐γ production after day 10 was concomitant with significant production of IL‐5 between 2 and 3 weeks post infection. In contrast, spleen cells from susceptible A/J mice produced high levels of IL‐5 within the first week of infection. In addition, these animals were found to have high serum levels of IL‐5. These results, thus, confirm previous observations that resolution of primary blood‐stage P. chabaudi infection occurs by sequential activation of Th1 CD4 + T cells followed by activation of the Th2 subset, and in addition, suggest that induction of a strong Th2 response early in infection may lead to a severe and lethal course of malaria.