Autor: |
Lion F. K. Uhl, Han Cai, Sophia L. Oram, Jagdish N. Mahale, Andrew J. MacLean, Julie M. Mazet, Theo Piccirilli, Alexander J. He, Doreen Lau, Tim Elliott, Audrey Gerard |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
|
Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-023-42455-4 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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