CD73+ memory CD4 T cells are a long-lived population with elevated effector function and prone to differentiate into TRM-like cells [ATAC-seq]

The understanding of heterogeneity of human memory T cells will help to know the function, development and maintenance of memory population, then to improve the recall response or effective immunotherapy. Ecto-5'-nucleotidase CD73 expression in four subsets of memory T cells decreases with aging. The resistance to apoptosis and high expression of IL7R entitle CD73+ memory T cells to be long-lived population. We found antigen-specific memory T cells have overwhelming CD73 expression. The transcriptional and chromatin accessibility profiles indicate the elevated effector functions in CD73+ memory CD4 T cells comparing to CD73- counterparts. Homer analysis and Transcriptional factor (TF)-regulatory element-target gene triplet network clearly show the crucial role of RUNT and NR family TFs in CD73+ cells. Furthermore, CD73+ memory CD4 T cells were prone to differentiate into TRM-like cells under in-vitro sequential TCR and TGF?/IL-15 signaling. The decreased percentage of CD73+ memory T cells with age leads to the less replenishment of TRM cells from peripheral blood. Overall design: Examine the difference of transcriptome and chromatin accessibility in two memory CD4 T cell subsets (CD73+ vs CD73-).