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10.1126/sciimmunol.aan8664

http://scihub22266oqcxt.onion/10.1126/sciimmunol.aan8664
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C5931334!5931334!29352091
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suck abstract from ncbi


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pmid29352091      Sci+Immunol 2018 ; 3 (19): ä
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  • Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis #MMPMID29352091
  • Patil VS; Madrigal A; Schmiedel BJ; Clarke J; O?Rourke P; de Silva AD; Harris E; Peters B; Seumois G; Weiskopf D; Sette A; Vijayanand P
  • Sci Immunol 2018[Jan]; 3 (19): ä PMID29352091show ga
  • CD4+ cytotoxic T lymphocytes (CD4-CTLs) have been reported to play a protective role in several viral infections. However, little is known in humans about the biology of CD4-CTL generation, their functional properties, and heterogeneity, especially in relation to other well-described CD4+ memory T cell subsets. We performed single-cell RNA sequencing in more than 9000 cells to unravel CD4-CTL heterogeneity, transcriptional profile, and clonality in humans. Single-cell differential gene expression analysis revealed a spectrum of known transcripts, including several linked to cytotoxic and costimulatory function that are expressed at higher levels in the TEMRA (effector memory T cells expressing CD45RA) subset, which is highly enriched for CD4-CTLs, compared with CD4+ T cells in the central memory (TCM) and effector memory (TEM) subsets. Simultaneous T cell antigen receptor (TCR) analysis in single cells and bulk subsets revealed that CD4-TEMRA cells show marked clonal expansion compared with TCM and TEM cells and that most of CD4-TEMRA were dengue virus (DENV)?specific in donors with previous DENV infection. The profile of CD4-TEMRA was highly heterogeneous across donors, with four distinct clusters identified by the single-cell analysis. We identified distinct clusters of CD4-CTL effector and precursor cells in the TEMRA subset; the precursor cells shared TCR clonotypes with CD4-CTL effectors and were distinguished by high expression of the interleukin-7 receptor. Our identification of a CD4-CTL precursor population may allow further investigation of how CD4-CTLs arise in humans and, thus, could provide insights into the mechanisms that may be used to generate durable and effective CD4-CTL immunity.
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