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Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8+T cells

Delpoux, A., Michelini, R.H., Verma, S., Lai, C.-Y., Omilusik, K.D., Utzschneider, D.T., Redwood, A.J., Goldrath, A.W., Benedict, C.A. and Hedrick, S.M. (2017) Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8+T cells. The Journal of Experimental Medicine, 215 (2). pp. 575-594.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Rockefeller University Press
Copyright: © 2018 Delpoux et al.
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