CD4 T cells display a spectrum of recall dynamics during re-infection with malaria parasites

Hyun Jae Lee; Marcela L Moreira; Shihan Li; Takahiro Asatsuma; Cameron G Williams; Oliver P Skinner; Saba Asad; Michael Bramhall; Zhe Jiang; Zihan Liu; Ashlyn S Kerr; Jessica A Engel; Megan SF Soon; Jasmin Straube; Irving Barrera; Evan Murray; Fei Chen; Jason Nideffer; Prasanna Jagannathan; Ashraful Haque

Journal article

CD4 T cells display a spectrum of recall dynamics during re-infection with malaria parasites

Hyun Jae Lee, Marcela L Moreira, Shihan Li, Takahiro Asatsuma, Cameron G Williams, Oliver P Skinner, Saba Asad, Michael Bramhall, Zhe Jiang, Zihan Liu, Ashlyn S Kerr, Jessica A Engel, Megan SF Soon, Jasmin Straube, Irving Barrera, Evan Murray, Fei Chen, Jason Nideffer, Prasanna Jagannathan, Ashraful Haque

Nature Communications | Nature Portfolio | Published : 2024

DOI: 10.1038/s41467-024-49879-6

Abstract

Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4+ T cell subsets remain unresolved. Here, we examine antigen-experienced CD4+ T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic TEM cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with TCM/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4+ T cells e..

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University of Melbourne Researchers

Josh Lee Author

Marcela De Lima Moreira Author

Shihan Li Author

Ollie Skinner Author

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Grants

Awarded by LIEF HPC-GPGPU Facility hosted at the University of Melbourne

Awarded by Australian National Health & Medical Research Council

Funding Acknowledgements

This research was supported by The University of Melbourne's Research Computing Services, the Petascale Campus Initiative, and the LIEF HPC-GPGPU Facility hosted at the University of Melbourne. This Facility was established with the assistance of LIEF Grant LE170100200. We thank the Biological Research Facility at the Peter Doherty Institute, the Doherty Institute node of the Melbourne Cytometry Platform. This work was funded by grants awarded to A.H. by the Australian National Health & Medical Research Council: Project/Ideas Grant Numbers 1126399, 1180951 and 2010784. Figures 1A, 2A, 6B and 7G were created with BioRender.com, released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.