ArticlePLoS pathogens2016
Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
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- Synergistic blockade of TIGIT and PD-L1 increases type-1 inflammation and improves parasite control during murine blood-stageInfection and immunity · 2024Article
- Antimicrobial activity of NK cells to Trypanosoma cruzi infected human primary Keratinocytes.PLoS neglected tropical diseases · 2024Article
- Chronic malaria exposure is associated with inhibitory markers on T cells that correlate with atypical memory and marginal zone-like B cells.Clinical and experimental immunology · 2024Article
- Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets.Nature communications · 2023Article
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- A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus.PLoS neglected tropical diseases · 2023Article
- A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.Frontiers in immunology · 2023Article
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- Preclinical Study ofCells · 2022Article
- Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer.Clinical and experimental immunology · 2022Article
- Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria.Molecular systems biology · 2022Article
- Erratum: Type 1 regulatory T cell-mediated tolerance in health and disease.Frontiers in immunology · 2022Article
- Type 1 regulatory T cell-mediated tolerance in health and disease.Frontiers in immunology · 2022Review
- PD-1Frontiers in immunology · 2022Article
- Increased Expression of Multiple Co-Inhibitory Molecules on Malaria-Induced CD8Frontiers in immunology · 2022Article
- Immunosuppression in Malaria: DoPathogens (Basel, Switzerland) · 2021Review
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- Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting.Malaria journal · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In acute Plasmodium falciparum (P. falciparum) malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.
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