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<p>Dengue virus (DENV) is a major global health threat, with secondary heterotypic infections potentially inducing detrimental memory immune responses. Antigen-specific CD8 + T cells contribute to both protection and pathogenicity, yet how their phenotypic heterogeneity relates to disease severity remains unclear. Here, we performed plate-based single-cell RNA sequencing of circulating DENV-specific CD8 + T cells identified by HLA tetramers loaded with DENV NS3-derived epitopes. Using tetramer binding to peptides corresponding to the currently and serologically inferred dominant previously infecting serotypes, we identify distinct CD8 + T cell subsets associated with disease severity. Asymptomatic dengue is enriched for lower tetramer binding cells with moderate cytotoxic programs, whereas dengue hemorrhagic fever is associated with high tetramer binding CX3CR1 + CD8 + T cells exhibiting enhanced expression of genes related to T cell receptor signaling and cytotoxicity. T cell receptor repertoires are similar among symptomatic cases but displayed temporal dynamics. Overall, DENV NS3-specific CD8 + T cells across disease severity and time are associated with distinct transcriptomic states and T cell receptor features.</p>

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Heterogeneity and dynamics of DENV-specific CD8 + T cells in dengue infection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月3日

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  • Sirawit Srikor,
  • Waradon Sungnak,
  • Chawinya Trakoolsoontorn,
  • Tiraput Poonpanichakul,
  • Natnicha Jiravejchakul,
  • Damita Jevapatarakul,
  • Narita Thungsatianpun,
  • Anunya Opasawatchai,
  • Lisa Dratva,
  • Lorenz Kretschmer,
  • Anavaj Sakuntabhai,
  • Pratap Singhasivanon,
  • Swangjit Suraamornkul,
  • Tawatchai Yingtaweesak,
  • Khajohnpong Manopwisedjaroen,
  • Nada Pitabut,
  • Sasikanya Thaloengsok,
  • Pattarakul Pakchotanon,
  • Oranart Matangkasombut,
  • Gavin Screaton,
  • Wanwisa Dejnirattisai,
  • Thaneeya Duangchinda,
  • Jongeun Park,
  • Kerstin Meyer,
  • Juthathip Mongkolsapaya,
  • Varodom Charoensawan,
  • Sarah A. Teichmann,
  • Ponpan Matangkasombut

摘要

Dengue virus (DENV) is a major global health threat, with secondary heterotypic infections potentially inducing detrimental memory immune responses. Antigen-specific CD8 + T cells contribute to both protection and pathogenicity, yet how their phenotypic heterogeneity relates to disease severity remains unclear. Here, we performed plate-based single-cell RNA sequencing of circulating DENV-specific CD8 + T cells identified by HLA tetramers loaded with DENV NS3-derived epitopes. Using tetramer binding to peptides corresponding to the currently and serologically inferred dominant previously infecting serotypes, we identify distinct CD8 + T cell subsets associated with disease severity. Asymptomatic dengue is enriched for lower tetramer binding cells with moderate cytotoxic programs, whereas dengue hemorrhagic fever is associated with high tetramer binding CX3CR1 + CD8 + T cells exhibiting enhanced expression of genes related to T cell receptor signaling and cytotoxicity. T cell receptor repertoires are similar among symptomatic cases but displayed temporal dynamics. Overall, DENV NS3-specific CD8 + T cells across disease severity and time are associated with distinct transcriptomic states and T cell receptor features.