Details

Autor(en) / Beteiligte

• Soon, Megan S F
• Lee, Hyun Jae
• Engel, Jessica A
• Straube, Jasmin
• Thomas, Bryce S
• Pernold, Clara P S
• Clarke, Lachlan S
• Laohamonthonkul, Pawat
• Haldar, Rohit N
• Williams, Cameron G
• Lansink, Lianne I M
• Moreira, Marcela L
• Bramhall, Michael
• Koufariotis, Lambros T
• Wood, Scott
• Chen, Xi
• James, Kylie R
• Lönnberg, Tapio
• Lane, Steven W
• Belz, Gabrielle T
• Engwerda, Christian R
• Khoury, David S
• Davenport, Miles P
• Svensson, Valentine
• Teichmann, Sarah A
• Haque, Ashraful

Titel

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

Ist Teil von

• Nature immunology, 2020-12, Vol.21 (12), p.1597-1610

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (T 1) and follicular helper T (T ) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T 1 and T trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T and central memory were revealed, with antimalarials modulating these responses and boosting T 1 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/ ).