Heterogeneity and dynamics of DENV-specific CD8 + T cells in dengue infection
- 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
2026-06-03
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.