2017
DOI: 10.1038/s41467-017-01728-5
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Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA

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 ba… Show more

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Cited by 216 publications
(231 citation statements)
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“…TEMRA cells showed a distinct transcriptional profile characterized by high expression of cytotoxic genes (eg. PRF1, CCL4, GZMA, GZMH), consistent with previous observations 25 . Importantly, these cells expressed comparable levels of CD4 and no CD8.…”
Section: (Methods Andsupporting
confidence: 93%
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“…TEMRA cells showed a distinct transcriptional profile characterized by high expression of cytotoxic genes (eg. PRF1, CCL4, GZMA, GZMH), consistent with previous observations 25 . Importantly, these cells expressed comparable levels of CD4 and no CD8.…”
Section: (Methods Andsupporting
confidence: 93%
“…These observations highlight the remarkable plasticity of CD4+ T cells and suggest that memory cells retain the ability to respond to cytokines. However, understanding the effects of cytokines on memory T cells is challenging because circulating memory T cells are heterogeneous, comprised of multiple subpopulations such as central and effector memory cells [24][25][26] .…”
mentioning
confidence: 99%
“…CD4 CTLs have been identified in differentiated T-cell subsets: i.e., effector memory (TEM) and effector memory re-expressing CD45RA (TEMRA) cells, which are often associated with a distinct surface phenotype including CCR7-, CD27-, CD28-, and CD11A+ (31, 32). To understand the CD4+GZMB+ T-cells in the context of differentiation, we constructed single-cell trajectories using the Monocle 2 (version 2.4.0) R package (33); all T cells in TC1 and TC2 were placed on these trajectories based on changes in their transcriptomes (Figs.…”
Section: Resultsmentioning
confidence: 99%
“…The primary function of CD4 T-cells, generally called helper T cells, is the regulation of immune responses using various cytokines, rather than direct elimination of target cells using cytotoxic molecules. Nevertheless, the presence of CD4 T-cells with cytotoxic features, namely CD4 CTLs, has been repeatedly reported in humans and mice (31, 32, 35). The reported fractions of CD4 CTLs are generally as low as a few percent of the total CD4 T-cells in healthy PBMCs (31, 36), whereas the size of the CD4 CTL fraction in the supercentenarians analyzed was on average 25% of T-cells, as measured by RNA-Seq and supported by the independent FACS measurements (Figs.…”
Section: Discussionmentioning
confidence: 99%
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