Continuous Activity of Foxo1 is Required to Prevent Anergy and Maintain the Memory State of CD8 T Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2017 Dec 29

PMID 29282254

Citations 49

Authors

Arnaud Delpoux

Rodrigo Hess Michelini

Shilpi Verma

Chen-Yen Lai

Kyla D Omilusik

Daniel T Utzschneider

Alec J Redwood

Ananda W Goldrath

Chris A Benedict

Stephen M Hedrick

Affiliations

Soon will be listed here.

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.

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