Interleukin-2 reverses T cell unresponsiveness to Plasmodium falciparum-antigen in malaria immune subjects

Chizzolini, Carlo; Geinoz, Anne; Schrijvers, Dirk

doi:10.1016/0008-8749(90)90001-8

Cited by 14 publications

(7 citation statements)

References 24 publications

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“…Depressed responses in highly exposed individuals can be rescued by supplementation of exogenous IL-2 [203]. Furthermore, these defective responses appear to be antigen-specific [194,202], suggesting clonal elimination or specific suppression by regulatory T cells [204,205].…”

Section: Dynamics Of Ifn-␥ Responses In Relation To Exposurementioning

confidence: 94%

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

McCall

Sauerwein

2010

Journal of Leukocyte Biology

141

113

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Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage parasites has generally been ascribed to humoral responses. A number of recent studies, however, have highlighted the existence of cellular immunity against blood-stage parasites, in particular, the prominence of IFN-γ production. Here, we have undertaken to chart the contribution of this prototypical cellular cytokine to immunity against pre-erythrocytic and blood-stage parasites. We summarize the various antiparasitic effector functions that IFN-γ serves to induce, review an array of data about its protective effects, and scrutinize evidence for any deleterious, immunopathological outcome in malaria patients. We discuss the activation and contribution of different cellular sources of IFN-γ production during malaria infection and its regulation in relation to exposure. We conclude that IFN-γ forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites and identify a number of implications for rational malaria vaccine development.

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Section: Dynamics Of Ifn-␥ Responses In Relation To Exposurementioning

confidence: 94%

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

McCall

Sauerwein

2010

Journal of Leukocyte Biology

141

113

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“…Increased levels of plasma IL-2 receptors were reported as being associated both with age and malaria parasitaemia in asymptomatic individuals (Riley et al 1993) and were found to be increased in acute P. falciparum infections (Kremsner et al 1990, Riley et al 1993). In addition, both the observations of a defect in IL-2 production in patients with acute malaria (Ho et al 1988) and that of increased T cell responses following addition of IL-2 to PBMC (Troye-Blomberg et al 1985, Chizzolini et al 1990) suggest a critical role for this cytokine. Therefore, we propose that one possible explanation for this observation might be linked with the consistent decrease in mononuclear cell apoptosis levels found associated with the addition of this cytokine, in parallel with increased T cell activation.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection

Balde¹,

Aribot²,

Tall

et al. 2000

Parasite Immunology

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In endemic areas, asymptomatic infection by the malaria parasite Plasmodium falciparum was found associated with elevated percentages of human host's mononuclear cell spontaneous in-vitro apoptosis. In Dielmo, a village where malaria is holoendemic, apoptosis was age-and parasite-dependent. In-vitro exposure of peripheral blood mononuclear cells (PBMC) to the parasite extract induced a marked increase in the mononuclear cell membrane expression of functional CD95 antigen: a 3-h exposure of the mononuclear cells to anti-CD95 antibodies led to a detectable increase in the mean percentage of apoptotic nuclei found in the cultures carried out in the presence of P. falciparum extracts compared to control cultures. IL-2, IL-4, IL-6 and IL-10 promoted the viability of PBMC in cultures while IL-1alpha or IFN-gamma had no obvious impact and TNFalpha gave conflicting results. IL-2 was the most efficient cytokine at rescuing PBMC from cell death and this effect was associated with a strong increase in T cell activation. In contrast, IL-4 and IL-10 had no such effect on T cell activation, hence they acted as survival factors and not through their mitogenic activity. Taken together, these different observations suggested that the levels of in-vitro apoptosis observed were not only associated with parasite infection, but also potentially modulated by the human host through different pathways.

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“…This question would be particularly relevant for vaccine development, since future vaccine constructs are likely to consist of repetitive epitopes, together with T cell epitopes, to allow the boosting effect provided by subsequent contacts with the parasite. Recent data suggest that lymphocytes from many individuals living in malaria-endemic areas show poor proliferative responses when challenged in vitro with P. falciparum or P. vivax crude or genetically engineered antigens [4,14,17,27]. The question of whether these plasmodial antigens or epitopes will be sufficiently immunogenic in human beings at a degree capable to confer immune protection, will be solved when vaccination trials using those antigens are carried out in endemic areas.…”

Section: Discussionmentioning

confidence: 99%

Reduced antibody response to the repetitive sequence of the Plasmodium falciparum circumsporozoite protein in mice infected with Plasmodium yoelii blood forms

Grillot

Pessi²,

Verdini³

et al. 1990

Med Microbiol Immunol

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The immunogenicity of the carrier-free synthetic peptide, (NANP)40, from the repetitive region of the Plasmodium falciparum circumsporozoite (CS) protein was investigated in genetically responder mice (C57BL/6, H-2b) acutely infected with blood forms of the non-lethal murine malaria parasite, P. yoelii. As compared to non-infected mice, P. yoelii-infected C57BL/6 mice produced significantly lower titers of anti-(NANP)40 IgG antibodies. This decrease in the anti-(NANP)40 antibody response peaked with the peak of parasitemia, and involved all the IgG subclasses. Interestingly, this P. yoelii-mediated effect was evident both on the development of the antibody response to the (NANP)40 peptide, and on an already established anti-(NANP)40 antibody titer, as seen in mice immunized with the peptide 1 month before the infection. Since (NANP)n-based constructs are strongly envisaged as potential vaccines against falciparum malaria, these results might be important in the evaluation of the efficacy of these vaccine candidates, when they will be used in individuals living in endemic areas.

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Interleukin-2 reverses T cell unresponsiveness to Plasmodium falciparum-antigen in malaria immune subjects

Cited by 14 publications

References 24 publications

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection

Reduced antibody response to the repetitive sequence of the Plasmodium falciparum circumsporozoite protein in mice infected with Plasmodium yoelii blood forms

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