Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype.

Frumento, Guido and Verma, Kriti and Croft, Wayne and White, Andrea and Zuo, Jianmin and Nagy, Zsuzsanna and Kissane, Stephen and Anderson, Graham and Moss, Paul and Chen, Frederick E (2020) Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype. iScience, 23 (4). p. 100989. ISSN 2589-0042. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Abstract

Primary stimulation of T cells is believed to trigger unidirectional differentiation from naive to effector and memory subsets. Here we demonstrate that IL-7 can drive the phenotypic reversion of recently differentiated human central and effector memory CD8 T cells into a naive-like phenotype. These "naive-revertant" cells display a phenotype similar to that of previously reported stem cell memory populations and undergo rapid differentiation and functional response following secondary challenge. The chromatin landscape of reverted cells undergoes substantial epigenetic reorganization with increased accessibility for cytokine-induced mediators such as STAT and closure of BATF-dependent sites that drive terminal differentiation. Phenotypic reversion may at least partly explain the generation of "stem cell memory" CD8 T cells and reveals cells within the phenotypically naive CD8 T cell pool that are epigenetically primed for secondary stimulation. This information provides insight into mechanisms that support maintenance of T cell memory and may guide therapeutic manipulation of T cell differentiation.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: WD Diseases and disorders of systemic, metabolic or environmental origin > WD350 Immunologic diseases
WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Mrs Yolande Brookes
Date Deposited: 03 Apr 2020 13:58
Last Modified: 03 Apr 2020 13:58
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2968

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