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 S. F. Soon, Jasmin Straube, Irving Barrera, Evan Murray, Fei Chen, Jason Nideffer, Prasanna Jagannathan and Ashraful Haque ()
Additional contact information
Hyun Jae Lee: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Marcela L. Moreira: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Shihan Li: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Takahiro Asatsuma: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Cameron G. Williams: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Oliver P. Skinner: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Saba Asad: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Michael Bramhall: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Zhe Jiang: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Zihan Liu: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Ashlyn S. Kerr: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity
Jessica A. Engel: QIMR Berghofer Medical Research Institute, Herston
Megan S. F. Soon: QIMR Berghofer Medical Research Institute, Herston
Jasmin Straube: QIMR Berghofer Medical Research Institute, Herston
Irving Barrera: Broad Institute of Harvard and MIT
Evan Murray: Broad Institute of Harvard and MIT
Fei Chen: Broad Institute of Harvard and MIT
Jason Nideffer: Stanford University
Prasanna Jagannathan: Stanford University
Ashraful Haque: University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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 exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4+ T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.

Date: 2024
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DOI: 10.1038/s41467-024-49879-6

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