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

Abstract

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 C57Bl/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-gamma), and of the Th2-derived cytokine, IL-5, using sandwich ELISAs. Spleen cells from resistant C57Bl/6 mice were found to produce high levels of IFN-gamma 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 IFN-gamma while both CD4+ and CD8+ T cells were found to produce IL-5. Decreased IFN-gamma 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.

T Cell-Intrinsic Factors Contribute to the Differential Ability of CD8+ T Cells To Rapidly Secrete IFN-γ in the Absence of Antigen

“…In many infection models, B6 mice are considered Th1 responders because they mount a strong IFN-g-secreting T cell response, and BALB/c mice are thought of as Th2 responders that typically produce more IL-10-secreting T cells (46)(47)(48). In these models, the differential ability of APCs to secrete IL-4 and IL-12 following pathogen encounter is thought to create polarized microenvironments that drive the differentiation of naive CD4 + T cells into either Th1 or Th2 cells (30,49).…”

Investigation of memory responses following Plasmodium chabaudi AS infection in mice distinct in susceptibility to clinical malaria

“…C57BL/6 mice mount a Th1 response early after infection, resulting in a moderate level of parasitemia and anemia and resolution of infection (Stevenson and Tam 1993). When most parasites have been eliminated from the circulation, the response switches, and interleukin (IL)-4-producing T cells predominate.…”

Expression, Purification, and Characterization of the Immunological Response to a 40-KilodaltonPlasmodium vivaxTryptophan-Rich Antigen

“…It is possible that cytokines secreted by T cells after activation qualitatively influence the nature of the immune response. As in P. chabaudi (31,34), the immune response to blood-stage infection could involve sequential activation of Th1 and Th2 cytokine responses during the acute and chronic stages of infection, respectively. There is a general belief that Th2 cytokines predominating during the chronic stage of infection are important for antibody-mediated antimalarial immunity (15).…”