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

Srikor, Sirawit; Sungnak, Waradon; Trakoolsoontorn, Chawinya; Poonpanichakul, Tiraput; Jiravejchakul, Natnicha; Jevapatarakul, Damita; Thungsatianpun, Narita; Opasawatchai, Anunya; Dratva, Lisa; Kretschmer, Lorenz; Pakchotanon, Pattarakul; Thaloengsok, Sasikanya; Pitabut, Nada; Manopwisedjaroen, Khajohnpong; Yingtaweesak, Tawatchai; Suraamornkul, Swangjit; Singhasivanon, Pratap; Sakuntabhai, Anavaj; Matangkasombut, Oranart; Screaton, Gavin

doi:10.1038/s41467-026-73491-5

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

Author(s)

Srikor, Sirawit

Sungnak, Waradon

Trakoolsoontorn, Chawinya

Poonpanichakul, Tiraput

Jiravejchakul, Natnicha

Jevapatarakul, Damita

Thungsatianpun, Narita

Opasawatchai, Anunya

Dratva, Lisa

Kretschmer, Lorenz

Pakchotanon, Pattarakul

Thaloengsok, Sasikanya

Pitabut, Nada

Manopwisedjaroen, Khajohnpong

Yingtaweesak, Tawatchai

Suraamornkul, Swangjit

Singhasivanon, Pratap

Sakuntabhai, Anavaj

Matangkasombut, Oranart

Screaton, Gavin

Dejnirattisai, Wanwisa

Duangchinda, Thaneeya

Park, Jongeun

Meyer, Kerstin

Mongkolsapaya, Juthathip

Charoensawan, Varodom

Teichmann, Sarah A.

Matangkasombut, Ponpan

Date Issued

December 1, 2026

Type

Article

DOI

10.1038/s41467-026-73491-5

Abstract

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.

Citation

Nature Communications, 17(1), 2026