Human memory T cell subsets share a core gene expression program defining memory as well as subset-specific gene modules related to effector functions and self-renewal
Date:
Flash talk given at annual Emory DSAC conference on Memory T cell project
Abstract
One of the defining features of the adaptive immune system is the ability to mount a secondary immune response in the event of re-exposure to antigen or after vaccination. These secondary immune responses, considered the “memory” of the immune system, have been observed as being greater in magnitude, faster, and more sensitive to antigen than the initial primary immune response. To accomplish the impressive feat of memory the immune system relies on a specific population of T cells termed memory cells. These cells are not homogenous and can be categorized into smaller subsets based on unique cell surface proteins and functional specializations. Traditionally, the two largest subsets of memory T cells are termed central memory (Tcm) and effector memory (Tem). These two categories were first identified and described by differences in expression of CCR7 and CD62L, two cell surface proteins which are both highly expressed in Tcm and naive T cells that enable cellular homing to secondary lymphoid organs. In this study we investigated transcriptional differences between circulating human CD4 and CD8 Tcm, Tem, and terminally differentiated effector (Temra) CD8 T cells on a genome-wide scale. Clustering gene expression modules identified a small core set of genes highly expressed in both resting Tcm and Tem cells (but not in naïve or terminally differentiated T cells) which was enriched for IL2 productrion, T cell receptor signaling, and costimuation related genes. Additionally, each subset expressed high levels of unique gene modules enabling specialized functions such as cell cytotoxicity or enhanced self-renewal.