ArticlePLoS pathogens2018
Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Memory regulatory T cells reprogram into protective TNature immunology · 2026Article
- Cellular Immune Response and T Cell Epitope Mapping ofVaccines · 2026Article
- Different clinical forms of Plasmodium vivax infection result in unique T cell epitope-specific immune responses.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Cellular and molecular interactions underlying the peripheral immune responses to blood-stage malaria infections.ImmunoHorizons · 2026Review
- Scalable nonparametric clustering with unified marker gene selection for single-cell RNA-seq data.Cell reports methods · 2026Article
- Scalable nonparametric clustering with unified marker gene selection for single-cell RNA-seq data.bioRxiv : the preprint server for biology · 2025Article
- PARP1-NFATc1-PD1 pathway of maturation and stability of CD8iScience · 2025Article
- Heightened innate immune state induced by viral vector leads to enhanced response to challenge and prolongs malaria vaccine protection.iScience · 2024Article
- Immune gene expression changes more during a malaria transmission season than between consecutive seasons.Microbiology spectrum · 2024Article
- IL-15 Complex-Induced IL-10 Enhances Plasmodium-specific CD4+ T Follicular Helper Differentiation and Antibody Production.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Immune Control in RepeatedOpen forum infectious diseases · 2024Article
- IL-27 produced during acute malaria infection regulates Plasmodium-specific memory CD4EMBO molecular medicine · 2023Article
- Cytolytic circumsporozoite-specific memory CD4Nature communications · 2023Article
- Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII).Parasites & vectors · 2023Article
- Effects of Low-Level Persistent Infection on Maintenance of Immunity by CD4 T Cell Subsets and Th1 Cytokines.Infection and immunity · 2023Article
- Characterization of NKG2-A/-C, Kir and CD57 on NK Cells Stimulated with pp65 and IE-1 Antigens in Patients Awaiting Lung Transplant.Life (Basel, Switzerland) · 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
- Using two phases of the CD4 T cell response to blood-stage murine malaria to understand regulation of systemic immunity and placental pathology in Plasmodium falciparum infection.Immunological reviews · 2020Review
- Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Protection at the peak of Plasmodium chabaudi blood-stage malaria infection is provided by CD4 T cells. We have shown that an increase in Th1 cells also correlates with protection during the persistent phase of malaria; however, it is unclear how these T cells are maintained. Persistent malaria infection promotes protection and generates both effector T cells (Teff), and effector memory T cells (Tem). We have previously defined new CD4 Teff (IL-7Rα-) subsets from Early (TeffEarly, CD62LhiCD27+) to Late (TeffLate, CD62LloCD27-) activation states. Here, we tested these effector and memory T cell subsets for their ability to survive and protect in vivo. We found that both polyclonal and P. chabaudi Merozoite Surface Protein-1 (MSP-1)-specific B5 TCR transgenic Tem survive better than Teff. Surprisingly, as Tem are associated with antigen persistence, Tem survive well even after clearance of infection. As previously shown during T cell contraction, TeffEarly, which can generate Tem, also survive better than other Teff subsets in uninfected recipients. Two other Tem survival mechanisms identified here are that low-level chronic infection promotes Tem both by driving their proliferation, and by programming production of Tem from Tcm. Protective CD4 T cell phenotypes have not been precisely determined in malaria, or other persistent infections. Therefore, we tested purified memory (Tmem) and Teff subsets in protection from peak pathology and parasitemia in immunocompromised recipient mice. Strikingly, among Tmem (IL-7Rαhi) subsets, only TemLate (CD62LloCD27-) reduced peak parasitemia (19%), though the dominant memory subset is TemEarly, which is not protective. In contrast, all Teff subsets reduced peak parasitemia by more than half, and mature Teff can generate Tem, though less. In summary, we have elucidated four mechanisms of Tem maintenance, and identified two long-lived T cell subsets (TemLate, TeffEarly) that may represent correlates of protection or a target for longer-lived vaccine-induced protection against malaria blood-stages.
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