Tags

Type your tag names separated by a space and hit enter

Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype.
iScience. 2020 Mar 19; 23(4):100989.I

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.

Authors+Show Affiliations

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; NHS Blood and Transplant, Birmingham, UK.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Centre for Computational Biology, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.Technology Hub, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. Electronic address: p.moss@bham.ac.uk.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; NHS Blood and Transplant, Birmingham, UK; Clinical Haematology, Barts Health NHS Trust, London, UK; Blizard Institute, Queen Mary University London, London, UK. Electronic address: frederick.chen@nhs.net.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32240954

Citation

Frumento, Guido, et al. "Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells Into a "Naive-Memory" Phenotype." IScience, vol. 23, no. 4, 2020, p. 100989.
Frumento G, Verma K, Croft W, et al. Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype. iScience. 2020;23(4):100989.
Frumento, G., Verma, K., Croft, W., White, A., Zuo, J., Nagy, Z., Kissane, S., Anderson, G., Moss, P., & Chen, F. E. (2020). Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype. IScience, 23(4), 100989. https://doi.org/10.1016/j.isci.2020.100989
Frumento G, et al. Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells Into a "Naive-Memory" Phenotype. iScience. 2020 Mar 19;23(4):100989. PubMed PMID: 32240954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homeostatic Cytokines Drive Epigenetic Reprogramming of Activated T Cells into a "Naive-Memory" Phenotype. AU - Frumento,Guido, AU - Verma,Kriti, AU - Croft,Wayne, AU - White,Andrea, AU - Zuo,Jianmin, AU - Nagy,Zsuzsanna, AU - Kissane,Stephen, AU - Anderson,Graham, AU - Moss,Paul, AU - Chen,Frederick E, Y1 - 2020/03/19/ PY - 2019/09/03/received PY - 2019/12/09/revised PY - 2020/03/11/accepted PY - 2020/4/3/pubmed PY - 2020/4/3/medline PY - 2020/4/3/entrez KW - Biological Sciences KW - Immunology KW - Molecular Biology SP - 100989 EP - 100989 JF - iScience JO - iScience VL - 23 IS - 4 N2 - 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. SN - 2589-0042 UR - https://www.unboundmedicine.com/medline/citation/32240954/Homeostatic_Cytokines_Drive_Epigenetic_Reprogramming_of_Activated_T_Cells_into_a_"Naive-Memory"_Phenotype L2 - https://linkinghub.elsevier.com/retrieve/pii/S2589-0042(20)30173-5 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.