Journal article
Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8+T cells
The Journal of Experimental Medicine, Vol.215(2), pp.575-594
2017
Abstract
Upon infection with an intracellular pathogen, cytotoxic CD8+ T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of differentiation is determined, in part, by FOXO1, a transcription factor known to integrate extrinsic input in order to specify survival, DNA repair, self-renewal, and proliferation. At issue is whether the state of T cell differentiation is specified by initial conditions of activation or is actively maintained. To study the spectrum of T cell differentiation, we have analyzed an infection with mouse cytomegalovirus, a persistent-latent virus that elicits different cytotoxic T cell responses characterized as acute resolving or inflationary. Our results show that FOXO1 is continuously required for all the phenotypic characteristics of memory-effector T cells such that with acute inactivation of the gene encoding FOXO1, T cells revert to a short-lived effector phenotype, exhibit reduced viability, and manifest characteristics of anergy.
Details
- Title
- Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8+T cells
- Authors/Creators
- A. Delpoux (Author/Creator)R.H. Michelini (Author/Creator)S. Verma (Author/Creator)C.-Y. Lai (Author/Creator)K.D. Omilusik (Author/Creator)D.T. Utzschneider (Author/Creator)A.J. Redwood (Author/Creator)A.W. Goldrath (Author/Creator)C.A. Benedict (Author/Creator)S.M. Hedrick (Author/Creator)
- Publication Details
- The Journal of Experimental Medicine, Vol.215(2), pp.575-594
- Publisher
- Rockefeller University Press
- Identifiers
- 991005540431707891
- Copyright
- © 2018 Delpoux et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.127 T Cell Regulation
- Web Of Science research areas
- Immunology
- Medicine, Research & Experimental
- ESI research areas
- Immunology