Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory

Nat Immunol. 2020 Dec;21(12):1597-1610. doi: 10.1038/s41590-020-0800-8. Epub 2020 Oct 12.


The dynamics of CD4+ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4+ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (TH1) and follicular helper T (TFH) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated TH1 and TFH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between TFH and central memory were revealed, with antimalarials modulating these responses and boosting TH1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4+ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations ( ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antimalarials / pharmacology
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Chromatin / genetics
  • Disease Models, Animal
  • Gene Expression Profiling
  • Humans
  • Immunologic Memory*
  • Malaria / immunology*
  • Malaria / parasitology
  • Malaria / therapy
  • Mice
  • Plasmodium / drug effects
  • Plasmodium / immunology*
  • Transcriptome*


  • Antimalarials
  • Biomarkers
  • Chromatin