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A CD4+ T cell reference map delineates subtype-specific adaptation during acute and chronic viral infections
- Source :
- eLife, Vol 11 (2022)
- Publication Year :
- 2022
- Publisher :
- eLife Sciences Publications Ltd, 2022.
-
Abstract
- CD4+ T cells are critical orchestrators of immune responses against a large variety of pathogens, including viruses. 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. Using single-cell transcriptomics, we characterized the diversity of CD4+ T cells responding to self-resolving and chronic viral infections in mice. We built a comprehensive map of virus-specific CD4+ T cells and their evolution over time, and identified six major cell states consistently observed in acute and chronic infections. During the course of acute infections, T cell composition progressively changed from effector to memory states, with subtype-specific gene modules and kinetics. Conversely, in persistent infections T cells acquired distinct, chronicity-associated programs. By single-cell T cell receptor (TCR) analysis, we characterized the clonal structure of virus-specific CD4+ T cells across individuals. Virus-specific CD4+ T cell responses were essentially private across individuals and most T cells differentiated into both Tfh and Th1 subtypes irrespective of their TCR. Finally, we showed that our CD4+ T cell map can be used as a reference to accurately interpret cell states in external single-cell datasets across tissues and disease models. 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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7a11d1e0d734fb28896b157112d9324
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.76339