Investigating Transcriptional Regulators of Memory T Follicular Helper Cells

Abstract

Abstract Generation of T-cell memory is crucial in conferring vaccine-induced immunity, particularly against pathogens where neutralizing antibodies alone are insufficient at providing long-term protection. While great advances have been made in understanding the generation and maintenance of memory CD8+ T cells and B cells, mechanisms underlying the generation of memory CD4+ T cells have remained relatively elusive. This limitation is in part due to the multi-potency and lineage plasticity exhibited by CD4+ T helper (TH) cells. Using the LCMV viral infection model, we show that the T follicular helper (TFH) subset are the predominant CD4+ memory T cell type based on its relative abundance following pathogen elimination as well as its multi-potent potential upon antigen re-challenge. This multi-potency of TFH memory cells during secondary challenge has also been observed in influenza infection and acute bacterial infection, suggesting that the TFH memory subset is most capable of providing a comprehensive and robust secondary response. From advancements in CD8+ memory T cell studies, it has become clear that transcription factors (TF) serve as crucial arbiters for the cell-fate decisions between short-lived effector and memory. To investigate the transcriptional mechanisms underlying TFH formation, we employed a novel bioinformatics analysis utilizing the PageRank algorithm that combines both RNA-seq and ATAC-seq and have identified putative transcriptional regulators of memory TFH differentiation. Further understanding of TFH memory formation will undoubtedly unveil new insights into CD4+ T cell memory in hopes of improving vaccine-based immunity.