Distinct features of a peripheral T-helper subset that drives B cell response in dengue virus infection
Abstract Dengue virus-induced humoral immunity can enhance the risk of severe disease, but the factors influencing this response are poorly understood. Here, we investigated the contribution of CD4+ T-cells in driving B-cell response in human dengue-infection. We identified a dominant peripheral PD1+ T-cell subset that aberrantly accumulated in severe patients and can induce B-cell differentiation via utilizing IL21 help-axis. Single-cell analyses uncovered the heterogeneity in peripheral PD1+ cells revealing the co-existence of subsets with ‘helper’ (IL21+) or ‘cytotoxic’ characteristics. The IL21+ subset displayed a distinct clonotypic and transcriptomic signature than Tfh cells and persist as memory in human lymph-nodes. Notably, we show the existence of extrafollicular B-cell responses in dengue that seems to controlled by IL21+-subset. Our study establishes peripheral IL21+-subset as a potential determinant of humoral response to DENV. These findings provide important insights into the T-cell-dependent regulation of humoral responses in dengue and inform the design of therapeutics and effective vaccines. One Sentence Summary: Peripheral IL21+ T helper subset is a major T-cell determinant of humoral immunity development to dengue virus in human infection..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 02. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gupta, Nimesh [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-3886693/v1 |
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| 520 | |a Abstract Dengue virus-induced humoral immunity can enhance the risk of severe disease, but the factors influencing this response are poorly understood. Here, we investigated the contribution of CD4+ T-cells in driving B-cell response in human dengue-infection. We identified a dominant peripheral PD1+ T-cell subset that aberrantly accumulated in severe patients and can induce B-cell differentiation via utilizing IL21 help-axis. Single-cell analyses uncovered the heterogeneity in peripheral PD1+ cells revealing the co-existence of subsets with ‘helper’ (IL21+) or ‘cytotoxic’ characteristics. The IL21+ subset displayed a distinct clonotypic and transcriptomic signature than Tfh cells and persist as memory in human lymph-nodes. Notably, we show the existence of extrafollicular B-cell responses in dengue that seems to controlled by IL21+-subset. Our study establishes peripheral IL21+-subset as a potential determinant of humoral response to DENV. These findings provide important insights into the T-cell-dependent regulation of humoral responses in dengue and inform the design of therapeutics and effective vaccines. One Sentence Summary: Peripheral IL21+ T helper subset is a major T-cell determinant of humoral immunity development to dengue virus in human infection. | ||
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