Journal article
Interferon-γ couples CD8+ T cell avidity and differentiation during infection
- Abstract:
- Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-023-42455-4
Authors
+ Kennedy Trust for Rheumatology Research
More from this funder
- Funding agency for:
- Gerard, A
- Grant:
- KENN151607
- KENN202112
+ Biotechnology and Biological Sciences Research Council
More from this funder
- Funding agency for:
- Gerard, A
- Grant:
- BB/R015651/1
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 14
- Article number:
- 6727
- Publication date:
- 2023-10-23
- Acceptance date:
- 2023-10-11
- DOI:
- EISSN:
-
2041-1723
- Language:
-
English
- Pubs id:
-
1552292
- Local pid:
-
pubs:1552292
- Deposit date:
-
2023-10-24
Terms of use
- Copyright holder:
- Uhl et al.
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Notes:
- This research was funded in whole or in part by the Biotechnology and Biological Sciences Research Council (BB/R015651/1). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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