Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi

Süss, Gabriele; Eichmann, Klaus; Kury, Evelyn; Linke, A; Langhorne, Jean

doi:10.1128/iai.56.12.3081-3088.1988

Cited by 112 publications

(61 citation statements)

References 38 publications

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“…Our data provide a clear association between an enhanced Th1 response and improved control of parasites in the bloodstream, particularly during PcAS infection. Previous reports, in which CD4 + T cells were depleted during PcAS infection, suggested that WT Th-cell responses did little to control the rate of parasite growth within the first week of infection, although they controlled the magnitude of peak parasitemia, and were certainly essential for resolution of infection [35,36]. Our data suggest that an enhanced Th1 response, in this case resulting from IRF7 or IFNAR1 deficiency, can reduce the rate of parasite growth within the first week of infection.…”

Section: Discussionmentioning

confidence: 94%

Spatiotemporal requirements for IRF7 in mediating type I IFN‐dependent susceptibility to blood‐stage Plasmodium infection

et al. 2014

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Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood-stage Plasmodium berghei ANKA (PbA) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. Interferon regulatory factor 7 (IRF7) is considered to be a master regulator of type I IFN responses. Here, we assessed IRF7 for its roles during lethal PbA infection and nonlethal Plasmodium chabaudi chabaudi AS (PcAS) infection as two distinct models of blood-stage malaria. We found that IRF7 was not essential for tissue accumulation of parasites, cerebral symptoms, or brain pathology. Using timed administration of anti-IFNAR1 mAb, we show that late IFNAR1 signaling promotes fatal disease via IRF7-independent mechanisms. Despite this, IRF7 significantly impaired early splenic Th1 responses and limited control of parasitemia during PbA infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal PcAS infection. Together, our data support a model in which IRF7 suppresses antiparasitic immunity in the spleen, while IFNAR1-mediated, but IRF7-independent, signaling contributes to pathology in the brain during experimental blood-stage malaria.Keywords: Cytokines r Immune regulation r Interferons r Malaria r T helper cells Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Ashraful Haque e-mail: ashraful.haque@qimrbergofer.edu.au * These authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 130-141 Immunity to infection 131 IntroductionType I IFNs are a family of closely related cytokines, widely known for their potent antiviral properties [1][2][3]. Recently, type I IFN, particularly IFN-β, has been used in the clinic to ameliorate the symptoms of multiple sclerosis, possibly via suppressive effects on T helper 1 (Th1) cells, although its precise mechanism of action remains unclear [4,5]. Type I IFN signaling occurs almost exclusively via the heterodimeric receptor, IFNAR1/2, which is widely expressed on hematopoietic and nonhematopoietic cells, although recent data also reveal IFNAR2-independent type I IFN signaling processes [6]. Most immune cells are capable of producing type I IFNs, including plasmacytoid dendritic cells (pDCs), which produce large amounts of these cytokines rapidly. Interferon regulatory factor 7 (IRF7) is a crucial transcription factor for driving type I IFN responses in mouse fibroblasts, pDCs, and conventional DCs (cDCs) in vitro, with concomitant severe defects in CD8 + T-cell priming and viral control in vivo [7]. Furthermore, IFN-α production by splenic pDCs and cDCs in vitro was completely dependent on IRF7, and independent of the closely related transcription factor, IRF3 [7]. Thus, IRF7 is often essential for driving type I IFN production, and IFNAR1-mediated signaling events. Consequently, IFNAR1-and IRF7 def...

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Section: Discussionmentioning

confidence: 94%

Spatiotemporal requirements for IRF7 in mediating type I IFN‐dependent susceptibility to blood‐stage Plasmodium infection

et al. 2014

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“…CD4 and CDS T lymphocytes are essential for the development of protective immunity to several infections (10)(11)(12). One of the functions of these cells is the production of IFN-y, a major T celllymphokine, which can also be produced by NK cells.…”

Section: Introductionmentioning

confidence: 99%

In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection

et al. 1992

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The possible role of interferon-gamma (IFN-y) in the resistance of A/J mice to MHV3 infection was investigated. Monoclonal antibodies specific for IFN-y, CD4 and CDS molecules were administered in vivo to deplete selectively the IFN -y synthesized or the appropriate subset of T cells. The animals were then infected with MHV3 and the course of infection was followed by studying different parameters, such as, the mortality, the virus growth in the tissues and the IFN-y synthesis in sera and peritoneal exudates. After MHV3 infection, a full resistance of control A/J mice was observed, in contrast to the high mortality rate observed among the depleted animals, where higher virus titers were found in different tissues. The IFN-y synthesis in sera and peritoneal exudates of depleted mice, after MHV3 infection, drastically decreased when compared to that detected in control mice. The data presented are consistent with the hypothesis that IFN-y plays an essential role in the resistance of A/J mice to MHV3 infection.

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“…Dockrell & Playfair 1983). CD4+ MHC class 11-restricted T cells are necessary to control a primary infection of P. chabaudi chabaudi (Suss et al 1988) and to transfer immunity to P. chabaudi adami (Cavacini, Long & Weidanz 1986;Brake et al 1988). Since CD4+ T cells are thought to be heterogeneous in their function (Mossman & Coffman 1987) it is necessary to delineate which of their effector capacities is important.…”

Section: Introductionmentioning

confidence: 99%

Limiting dilution analysis of the T cell response to Plasmodium chabaudi chabaudi in mice

Langhorne

Simon

1989

Parasite Immunology

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A limiting dilution assay system was developed in order to measure the in-vitro T cell response to antigens of the erythrocytic stages of Plasmodium chabaudi. The conditions of the assay are such that only CD4+ T cells are able to respond. The assay allows the determination of the frequencies of T cells which proliferate and/or which develop into helper cells for antibody production during a primary infection. A specific response from splenic T cells can be measured as early as 7 days after infection, and is still significant 3 months after injection of P. chabaudi. At all times the frequency of proliferating cells was greater than the precursor frequency of T helper cells. This suggests that a proportion of CD4+ T cells in this assay, although they respond to malarial antigen, do not develop into helper cells for antibody production. This limiting dilution assay will be a useful method by which to evaluate the functional heterogeneity of the CD4+ T cell response to malaria antigens.

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Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi

Cited by 112 publications

References 38 publications

Spatiotemporal requirements for IRF7 in mediating type I IFN‐dependent susceptibility to blood‐stage Plasmodium infection

Spatiotemporal requirements for IRF7 in mediating type I IFN‐dependent susceptibility to blood‐stage Plasmodium infection

In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection

Limiting dilution analysis of the T cell response to Plasmodium chabaudi chabaudi in mice

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