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Dengue-specific CD8+ T cell subsets display specialized transcriptomic and TCR profiles.

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The Journal of Clinical Investigation
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This study defines the molecular profiles of CD8+ T cells crucial for dengue virus (DENV) immunity. Understanding these T cell responses provides a benchmark for developing effective DENV vaccines.

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Area of Science:

  • Immunology
  • Virology
  • Genomics

Background:

  • CD8+ T cells are vital for protection against severe dengue virus (DENV) disease and vaccine effectiveness.
  • The specific molecular programs of DENV-specific CD8+ T cell subsets remain largely undefined.

Purpose of the Study:

  • To define the transcriptomic profiles of human DENV-specific CD8+ T cell subsets.
  • To characterize the activation and functional states of these T cells following antigen stimulation.
  • To identify unique T cell receptor features within DENV-specific CD8+ T cell subsets.

Main Methods:

  • Isolation and stimulation of human DENV-specific CD8+ T cells from multiply infected donors.
  • Transcriptomic profiling using RNA sequencing.
  • Analysis of T cell subsets, including effector memory (Tem) and effector memory re-expressing CD45RA (Temra) cells.
  • T cell receptor (TCR) repertoire analysis.

Main Results:

  • DENV-specific CD8+ T cells primarily comprised Tem and Temra subsets.
  • Upon antigen stimulation, these subsets exhibited distinct gene expression profiles, indicating full activation and polyfunctionality.
  • Despite being highly functional, the transcriptional responses were relatively narrow.
  • Unique TCR features, including gene usage, were observed in DENV-specific Tem and Temra cells.

Conclusions:

  • This study provides the first transcriptomic definition of activated human DENV-specific CD8+ T cell subsets.
  • The identified molecular and TCR profiles serve as a benchmark for evaluating and designing DENV vaccines.
  • Understanding these cellular responses is key to improving dengue vaccine efficacy.