%0 Journal Article
%T CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites.
%A Lee HJ
%A Moreira ML
%A Li S
%A Asatsuma T
%A Williams CG
%A Skinner OP
%A Asad S
%A Bramhall M
%A Jiang Z
%A Liu Z
%A Kerr AS
%A Engel JA
%A Soon MSF
%A Straube J
%A Barrera I
%A Murray E
%A Chen F
%A Nideffer J
%A Jagannathan P
%A Haque A
%J Nat Commun
%V 15
%N 1
%D 2024 Jun 28
%M 38944658
%F 17.694
%R 10.1038/s41467-024-49879-6
%X 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.