CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities

Tomasz Ahrends, Julia Busselaar, Tesa M. Severson, Nikolina Bąbała, Evert Vries, Astrid Bovens, Lodewyk Wessels, Fred Leeuwen and Jannie Borst ()
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Tomasz Ahrends: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Julia Busselaar: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Tesa M. Severson: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Nikolina Bąbała: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Evert Vries: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Astrid Bovens: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Lodewyk Wessels: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Fred Leeuwen: The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Jannie Borst: The Netherlands Cancer Institute-Antoni van Leeuwenhoek

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract CD4+ T cell help is required for the generation of CD8+ cytotoxic T lymphocyte (CTL) memory. Here, we use genome-wide analyses to show how CD4+ T cell help delivered during priming promotes memory differentiation of CTLs. Help signals enhance IL-15-dependent maintenance of central memory T (TCM) cells. More importantly, help signals regulate the size and function of the effector memory T (TEM) cell pool. Helped TEM cells produce Granzyme B and IFNγ upon antigen-independent, innate-like recall by IL-12 and IL-18. In addition, helped memory CTLs express the effector program characteristic of helped primary CTLs upon recall with MHC class I-restricted antigens, likely due to epigenetic imprinting and sustained mRNA expression of effector genes. Our data thus indicate that during priming, CD4+ T cell help optimizes CTL memory by creating TEM cells with innate and help-independent antigen-specific recall capacities.

Date: 2019
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DOI: 10.1038/s41467-019-13438-1

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