ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Early effector cells survive the contraction phase in malaria infection and generate both central and effector memory T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Trial
- Targeting T-Cell Activation for Malaria Immunotherapy: Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Bacteria-instructed B cells cross-prime naïve CD8EMBO reports · 2023Article
- Effects of Low-Level Persistent Infection on Maintenance of Immunity by CD4 T Cell Subsets and Th1 Cytokines.Infection and immunity · 2023Article
- Model of severe malaria in young mice suggests unique response of CD4 T cells.Parasite immunology · 2022Article
- Review
- 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
- Subsequent malaria enhances virus-specific T cell immunity in SIV-infected Chinese rhesus macaques.Cell communication and signaling : CCS · 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
- Acquired Clinical Immunity to Malaria in Nonhuman Primates Coinfected withInfection and immunity · 2022Article
- Transcriptome dynamics of CD4Nature immunology · 2020Article
- T Helper Plasticity Is Orchestrated by STAT3, Bcl6, and Blimp-1 Balancing Pathology and Protection in Malaria.iScience · 2020Article
- B cells are sufficient to prime the dominant CD4+ Tfh response to Plasmodium infection.The Journal of experimental medicine · 2020Article
- 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
- A Conserved TCRβ Signature Dominates a Highly Polyclonal T-Cell Expansion During the Acute Phase of a Murine Malaria Infection.Frontiers in immunology · 2020Article
- T cell-mediated immunity to malaria.Nature reviews. Immunology · 2019Review
- Development of B Cell Memory in Malaria.Frontiers in immunology · 2019Review
- Neddylation contributes to CD4+ T cell-mediated protective immunity against blood-stage Plasmodium infection.PLoS pathogens · 2018Article
- Early programming and late-acting checkpoints governing the development of CD4 T-cell memory.Immunology · 2018Review
- Th1-like Plasmodium-Specific Memory CD4Cell reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection.
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