Distinct features of a peripheral T helper subset that drives the B cell response in dengue virus infection
Dengue-virus-induced humoral immunity can increase the risk of severe disease, but the factors influencing this response are poorly understood. Here, we investigate the contribution of CD4<sup>+</sup> T cells to B cell responses in human dengue infection. We identify a dominant peripheral PD-1<sup>+</sup> T cell subset that accumulates in severe patients and could induce B cell differentiation via interleukin-21 (IL-21)-related pathway. Single-cell analyses reveal heterogeneity within PD-1<sup>+</sup> cells, demonstrating the coexistence of subsets with "helper" (IL-21<sup>+</sup>) or "cytotoxic" characteristics. The IL-21<sup>+</sup> subset displays a distinct clonotypic and transcriptomic signature compared to follicular helper T cells and persists as a memory in lymph nodes. Notably, we show that the IL-21<sup>+</sup> subset seems to majorly drive the extrafollicular B cell responses in dengue. Our study establishes the peripheral IL-21<sup>+</sup> subset as a potential determinant of the humoral response to dengue virus infection. These findings provide important insights into the T-cell-dependent regulation of humoral responses and can inform the design of effective dengue vaccines.
Authors
- Alessandro Sette (ORCID: https://orcid.org/0000-0001-7013-2250)
- Naveet Wig
- Manish Soneja (ORCID: https://orcid.org/0000-0002-8619-7929)
- Shilpa Sachan (ORCID: https://orcid.org/0009-0005-9809-4766)
- Kapil Sikka (ORCID: https://orcid.org/0000-0002-3457-4518)
- Jatin Ahuja (ORCID: https://orcid.org/0000-0002-3072-8735)
- Nimesh Gupta (ORCID: https://orcid.org/0000-0001-9433-8448)
- Debasisa Mohanty (ORCID: https://orcid.org/0000-0002-3374-0588)
- Daniela Weiskopf (ORCID: https://orcid.org/0000-0003-2968-7371)
- Bhushan Nikam
- Poonam Coshic (ORCID: https://orcid.org/0000-0002-4606-7417)
- V. Sureshkumar
- Bhanu Pratap Singh (ORCID: https://orcid.org/0000-0002-1757-9763)
- Vinod Kumar (ORCID: https://orcid.org/0000-0001-9089-4308)
- Asgar Ansari (ORCID: https://orcid.org/0000-0002-7073-1154)
- Shweta Jain
Institutions
- La Jolla Institute for Immunology (US)
- University of California San Diego (US)
- Institute for Transfusion Medicine (US)
- National Institute of Immunology (IN)
- All India Institute of Medical Sciences (IN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115366
- Citations
- 9
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 16.91
Funders
- Department of Biotechnology, Ministry of Science and Technology, India
- Department of Science and Technology, Ministry of Science and Technology, India
- National Institute of Informatics
- National Institutes of Health
- Science and Engineering Research Board