title: NFκB-Pim-1-Eomesodermin axis is critical for maintaining CD8 T-cell memory quality.
abstract: T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB-Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB-Pim-1-Eomes axis regulates Eomes levels to maintain memory fitness.
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.|Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Knudson
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Curtis J
authors.identifier: 0000-0001-5238-5086
authors.initials: CJ
authors.lastname: Pritzl
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Vikas
authors.initials: V
authors.lastname: Saxena
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121.
authors.forename: Amnon
authors.initials: A
authors.lastname: Altman
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Daniels
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212; teixeiropernase@missouri.edu.
authors.forename: Emma
authors.initials: E
authors.lastname: Teixeiro
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology*
chemical_list: D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D020825:T-Box Domain Proteins
keywords: CD8 T-cell memory; Eomesodermin; NFkB; Pim-1