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


Soon, MSF; Lee, HJ; Engel, JA; Straube, J; Thomas, BS; Pernold, CPS; Clarke, LS; Laohamonthonkul, P; Haldar, RN; Williams, CG; Lansink, LIM; Moreira, ML; Bramhall, M; Koufariotis, LT; Wood, S; Chen, X; James, KR; Lonnberg, T; Lane, SW; Belz, GT; Engwerda, CR; Khoury, DS; Davenport, MP; Svensson, V; Teichmann, SA; Haque, A
2020-10-12
Nature Immunology
Journal epub ahead of print
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 ( http://haquelab.mdhs.unimelb.edu.au/cd4_memory/ ).
NPG
Immunology
10.1038/s41590-020-0800-8
33046889
Refer to copyright notice on published article.

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Creation Date 2020-11-02 04:55:19 Last Modified 2020-11-03 09:29:22