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Dengue-specific CD8+ T cell subsets display specialized transcriptomic and TCR profiles
Yuan Tian, … , Bjoern Peters, Alessandro Sette
Yuan Tian, … , Bjoern Peters, Alessandro Sette
Published March 18, 2019
Citation Information: J Clin Invest. 2019;129(4):1727-1741. https://doi.org/10.1172/JCI123726.
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Research Article Immunology Infectious disease

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

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Abstract

Accumulating evidence demonstrates that CD8+ T cells contribute to protection from severe dengue virus (DENV) disease and vaccine efficacy. Nevertheless, molecular programs associated with DENV-specific CD8+ T cell subsets have not been defined. Here, we studied the transcriptomic profiles of human DENV-specific CD8+ T cells isolated after stimulation with DENV epitopes from donors who had been infected with DENV multiple times and would therefore be expected to have significant levels of adaptive immunity. We found that DENV-specific CD8+ T cells mainly consisted of effector memory subsets, namely CD45RA−CCR7− effector memory (Tem) and CD45RA+CCR7− effector memory re-expressing CD45RA (Temra) cells, which enacted specific gene expression profiles upon stimulation with cognate antigens. DENV-specific CD8+ T cell subsets in general, and Temra cells in particular, were fully activated and polyfunctional, yet associated with relatively narrow transcriptional responses. Furthermore, we found that DENV-specific CD8+ Tem and Temra cells showed some unique T cell receptor features in terms of overlap and variable (V) gene usage. This study provides a transcriptomic definition of DENV-specific activated human CD8+ T cell subsets and defines a benchmark profile that vaccine-specific responses could aim to reproduce.

Authors

Yuan Tian, Mariana Babor, Jerome Lane, Grégory Seumois, Shu Liang, N.D. Suraj Goonawardhana, Aruna D. De Silva, Elizabeth J. Phillips, Simon A. Mallal, Ricardo da Silva Antunes, Alba Grifoni, Pandurangan Vijayanand, Daniela Weiskopf, Bjoern Peters, Alessandro Sette

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Figure 1

DENV-specific CD8+ T cells are predominantly Tem and Temra cells.

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DENV-specific CD8+ T cells are predominantly Tem and Temra cells.
Human ...
Human PBMCs isolated from donors that had been infected with DENV multiple times were stimulated with DENV CD8+ T cell megapool, and DENV-specific CD8+ T cells were identified by the production of IFN-γ. (A) Gating strategy to identify and sort DENV-specific CD8+ Tem and Temra cells. (B) Flow cytometry plots (top) and bar graph (bottom) show the production of IFN-γ by CD8+ T cells (n = 6). (C) Flow cytometry plots (top) and bar graphs (bottom) show the expression of CD45RA and CCR7 by unstimulated IFN-γ– or DENV IFN-γ+ CD8+ T cells (n = 6). Error bars show median with interquartile range.
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