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Transcriptome Dynamics Reveals Progressive Transition from Effector to Memory in CD4^+ T cells

Soon, Megan S. F. and Lee, Hyun Jae and Engel, Jessica A. and Straube, Jasmin and Thomas, Bryce S. and Clarke, Lachlan S. and Laohamonthonkul, Pawat and Pernold, Clara P. S. and Haldar, Rohit N. and Williams, Cameron G. and Lansink, Lianne I. M. and Koufariotis, Ross and Lakis, Vanessa and Woody, Scott and Chen, Xi and James, Kylie R. and Lönnberg, Tapio and Lane, Steven W. and Davenport, Miles P. and Khoury, David S. and Svensson, Valentine and Teichmann, Sarah A. and Haque, Ashraful (2019) Transcriptome Dynamics Reveals Progressive Transition from Effector to Memory in CD4^+ T cells. . (Unpublished)

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CD4^+ T cells are repositories of immune memory, conferring enhanced immunity to many infectious agents. Studies of acute viral and bacterial infection suggest that memory CD4^+ T cells develop directly from effectors. However, delineating these dynamic developmental pathways has been challenging. Here, we used high-resolution single-cell RNA-seq and temporal mixture modelling to examine the fate of Th1 and Tfh effector cells during non-lethal Plasmodium infection in mice. We observed linear Th1 and Tfh pathways towards memory, characterised by progressive halving in the numbers of genes expressed, and partial transcriptomic coalescence. Low-level persisting infection diverted but did not block these pathways. We observed in the Th1-pathway a linear transition from Th1 through a Tr1 state to T_(EM) cells, which were then poised for Th1 re-call. The Tfh-pathway exhibited a modest Th1-signature throughout, with little evidence of Tr1 development, and co-expression of T_(CM) and memory Tfh markers. Thus, we present a high-resolution atlas of transcriptome dynamics for naïve to memory transitions in CD4^+ T cells. We also defined a subset of memory-associated genes, including transcription factors Id2 and Maf, whose expression increased progressively against the background of transcriptomic quiescence. Single-cell ATAC-seq revealed substantial heterogeneity in chromatin accessibility in single effectors, which was extensively, though incompletely reset and homogenised in memory. Our data reveal that linear transitions from effector to memory occur in a progressive manner over several weeks, suggesting opportunities for manipulating CD4^+ T cell memory after primary infection.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Chen, Xi0000-0003-2648-3146
Svensson, Valentine0000-0002-9217-2330
Teichmann, Sarah A.0000-0002-6294-6366
Alternate Title:Transcriptome Dynamics Reveals Progressive Transition from Effector to Memory in CD4+ T cells
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. The authors declare no conflicts of interest.
Record Number:CaltechAUTHORS:20190619-090153443
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Official Citation:Transcriptome Dynamics Reveals Progressive Transition from Effector to Memory in CD4+ T cells. Megan S. F. Soon, Hyun Jae Lee, Jessica A. Engel, Jasmin Straube, Bryce S. Thomas, Lachlan S. Clarke, Pawat Laohamonthonkul, Clara P. S. Pernold, Rohit N. Haldar, Cameron G. Williams, Lianne I. M. Lansink, Ross Koufariotis, Vanessa Lakis, ScottWood, Xi Chen, Kylie R. James, Tapio Lönnberg, Steven W. Lane, Miles P. Davenport, David S. Khoury, Valentine Svensson, Sarah A. Teichmann, Ashraful Haque. bioRxiv 675967; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:96518
Deposited By: Tony Diaz
Deposited On:19 Jun 2019 17:08
Last Modified:03 Oct 2019 21:23

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