Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice.
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.
Stevenson
M M
MM
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Tam
M F
MF
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003208:Concanavalin A; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008288:Malaria / Q000097:blood / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016788:Plasmodium chabaudi; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018800:Thy-1 Antigens; D013997:Time Factors
D000954:Antigens, Surface; D016827:CD8 Antigens; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018800:Thy-1 Antigens; D003208:Concanavalin A; D007371:Interferon-gamma