Cellular mechanisms in the immune response to malaria in Plasmodium vinckei-infected mice

Abstract

Infection of mice with the malaria parasite Plasmodium vinckei vinckei is 100% lethal. However, after two infections followed by drug cure, BALB/c mice develop a solid immunity which is antibody independent but mediated by CD4 ؉ T cells. To elucidate the mechanisms of this immunity, spleen cells from immune mice were challenged in vitro with lysates of P. vinckei-infected or uninfected erythrocytes. The parasite antigen induced proliferation of T cells from immune mice but not from nonimmune mice. When gamma interferon production by cells from immune mice was assayed at the single-cell level, 1 to 3 cells per 1,000 cells were found to release this cytokine when exposed to antigen. In contrast, the numbers of interleukin 4 (IL-4)-producing cells from both immune and control mice were <4 per 10 6 cells, regardless of antigen exposure. Investigation in a bioassay showed that P. vinckei antigen induced the release of IL-4 from spleen cells of immune mice but not from those of control mice. Nevertheless, that IL-4 is of minor significance in this system is also suggested by the absence of elevation of immunoglobulin E levels in blood samples from these mice, in contrast to what is seen with P. chabaudi infection, in which IL-4-producing Th2 cells are of major importance for immunity during later phases of infection. Taken together, the present results indicate that immunity to P. vinckei is a Th1 response, with gamma interferon being an important protective factor. Whether or not the Th1 response, through overproduction of tumor necrosis factor alpha, is also responsible for pathology and death in this infection remains to be clarified.

Protective immunity against malaria after vaccination

“…Protection was always associated with the induction of both Th1 and Th2 responses, Th1 responses preceding maximum activation of the Th2 response (24,25). This pattern of T-cell responses was also described in mice infected with attenuated nonlethal P. berghei (31) or with Plasmodium vinckei (32), in which Th1 subset activity was crucial for parasite elimination.…”

Elevated plasma levels of IgE in Plasmodium falciparum-primed individuals reflect an increased ratio of IL-4 to interferon-gamma (IFN-γ)-producing cells

“…In mice infected with the malaria parasite P. chabaudi chabaudi, clearance of the infection was associated with an initial Th1-type of response followed by a Th2 response associated with IgE elevation [9]. In contrast, in mice infected with the malaria parasite P. vinckei vinckei, immunity depends primarily on a Th1 response (IFN-g producing), and in such mice no IgE elevation was demonstrated [30]. In any event, IgE-mediated cellular reactions involving eosinophils, platelets or monocytes/macrophages (IgE-binding cells, equipped with Fce receptors) have been shown to efficiently kill helminthic parasites in vitro.…”

Reciprocal Regulation of Th1- and Th2-Cytokine-Producing T Cells during Clearance of Parasitemia inPlasmodium falciparumMalaria

“…Taking both Th1 and Th2 data together, a more pronounced Th2-driven response (a lower ratio of IFN-␥ expression to IL-4 expression) during acute untreated P. falciparum malaria was replaced by a shift towards a Th1-biased response (a higher ratio of IFN-␥ expression to IL-4 expression) paralleling the clearance of parasitemia in peripheral-blood T cells. High IFN-␥ production as part of a Th1-driven immune response has been associated with a more favorable outcome in most animal models of malaria (13,14,20,21,23,25), and treatment of the otherwiselethal murine Plasmodium vinckei infection with IFN-␥ greatly enhanced the effect of antimalarial chemotherapy (8,16,21). This effect has been attributed to the monocyte/macrophageactivating capacities of IFN-␥, with rapid killing of the malarial blood-stage parasites by reactive oxygen and nitrogen intermediates (1,27).…”