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CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites.
CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites. Nature communications Lee, H. J., Moreira, M. L., Li, S., Asatsuma, T., Williams, C. G., Skinner, O. P., Asad, S., Bramhall, M., Jiang, Z., Liu, Z., Kerr, A. S., Engel, J. A., Soon, M. S., Straube, J., Barrera, I., Murray, E., Chen, F., Nideffer, J., Jagannathan, P., Haque, A. 2024; 15 (1): 5497Abstract
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.
View details for DOI 10.1038/s41467-024-49879-6
View details for PubMedID 38944658
View details for PubMedCentralID PMC11214622