Abstract
The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.
Highlights
The expression of CD45RA is generally associated with naive T cells
CD4 TEMRA cells were associated with a higher level of variation, with TEMRA cells from some individuals overlapping with TEM cells, whereas TEMRA cells from others were more separated from CD4 TEM cells (Fig. 1b)
We showed that CD4 TEMRA cells are readily discernable from naive (TN) and other memory CD4 T-cell subsets including central memory (TCM) and effector memory (TEM) cells based on expression of CD45RA, CCR7, and heterogeneous nuclear ribonucleoprotein L-like (HNRPLL)
Summary
A subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. Accumulating studies have indicated that infections with pathogens such as human cytomegalovirus (CMV) and dengue virus (DENV) are associated with an expansion of CD4 TEMRA cells[7,8,9]. How CD4 TEMRA cells differ from other memory-phenotype CD4 T cells such as TCM and TEM cells at the global level is less well defined. It remains to be addressed whether CD4 TEMRA cells represent a homogenous population, or heterogeneity exists within this subset. In other donors, by comparison with their TCM and CCR7 a
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