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• W3201607317 abstract "Abstract CD4 + T cells are critical orchestrators of immune responses against a large variety of pathogens, including viruses. The multifaceted roles of CD4 + T cells, including their help to innate cells, CD8 + T and B cells and their support for long-lived immunity rely on a profound functional heterogeneity. While multiple CD4 + T cell subtypes and their key transcriptional regulators have been identified, there is a lack of consistent definition for CD4 + T cell transcriptional states. In addition, the progressive changes affecting CD4 + T cell subtypes during and after immune responses remain poorly defined. Taking advantage of single-cell transcriptomics, efficient computational methods, and robust animal models, we characterize the transcriptional landscape of CD4 + T cells responding to self-resolving and chronic viral infections. We build a comprehensive atlas of virus-specific CD4 + T cells and their evolution over time, and identify six major distinct cell states that are consistently observed in acute and chronic infections. During the course of acute infection, T cell composition progressively changes from effector to memory states, with subtype-specific gene modules and kinetics. Conversely, T cells in persistent infections fail to transition from effector to memory states, and acquire distinct, chronicity-associated transcriptional programs. By single-cell T cell receptor (TCR) sequencing analysis, we characterize the clonal structure of virus-specific CD4 + T cells across individuals and T cell subtypes. We find that virus-specific CD4 + T cell responses are mainly private across individuals and that most T cells differentiate into all subtypes independently of their TCR, in both acute and chronic infections. Finally, we show that our CD4 + T cell atlas can be used as a reference to accurately interpret cell states in external single-cell datasets. Overall, this study describes a previously unappreciated level of adaptation of the transcriptional states of CD4 + T cells responding to viruses and provides a new computational resource for CD4 + T cell analysis, available online at https://spica.unil.ch ." @default.
• W3201607317 created "2021-09-27" @default.
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• W3201607317 date "2021-09-20" @default.
• W3201607317 modified "2023-10-02" @default.
• W3201607317 title "A single-cell reference atlas delineates CD4+ T cell subtype-specific adaptation during acute and chronic viral infections" @default.
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• W3201607317 doi "https://doi.org/10.1101/2021.09.20.458613" @default.
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