{Reference Type}: Journal Article
{Title}: CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites.
{Author}: Lee HJ;Moreira ML;Li S;Asatsuma T;Williams CG;Skinner OP;Asad S;Bramhall M;Jiang Z;Liu Z;Kerr AS;Engel JA;Soon MSF;Straube J;Barrera I;Murray E;Chen F;Nideffer J;Jagannathan P;Haque A;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Jun 28
{Factor}: 17.694
{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 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.