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10.1126/sciimmunol.aan8664

http://scihub22266oqcxt.onion/10.1126/sciimmunol.aan8664
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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 PMID29352091 show 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 T(EMRA) (effector memory T cells expressing CD45RA) subset, which is highly enriched for CD4-CTLs, compared with CD4(+) T cells in the central memory (T(CM)) and effector memory (T(EM)) subsets. Simultaneous T cell antigen receptor (TCR) analysis in single cells and bulk subsets revealed that CD4-T(EMRA) cells show marked clonal expansion compared with T(CM) and T(EM) cells and that most of CD4-T(EMRA) were dengue virus (DENV)-specific in donors with previous DENV infection. The profile of CD4-T(EMRA) 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 T(EMRA) 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.
  • |CD4-Positive T-Lymphocytes/*immunology [MESH]
  • |Gene Expression Profiling/methods [MESH]
  • |Humans [MESH]
  • |Immunologic Memory/immunology [MESH]
  • |Leukocytes, Mononuclear/immunology [MESH]
  • |Lymphocyte Activation/immunology [MESH]
  • |Receptors, Antigen, T-Cell/immunology [MESH]
  • |Single-Cell Analysis/methods [MESH]
  • |T-Lymphocytes, Cytotoxic/*immunology [MESH]


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