title: Old Mice Accumulate Activated Effector CD4 T Cells Refractory to Regulatory T Cell-Induced Immunosuppression.
abstract: Chronic low-grade inflammation and reduced lymphocyte potency are implicated in the pathogenesis of major illnesses associated with aging. Whether this immune phenotype results from a loss of cell-mediated regulation or intrinsic dysregulated function of effector T cells (Teffs) requires further research. Here, we report that, as compared with young C57BL6 mice, old mice show an increased frequency of CD4+CD62L- Teffs with a dysregulated activated phenotype and markedly increased effector functions. Analysis of the frequency and suppressive function of CD4+FoxP3+ regulatory T cells (Tregs) indicates an increase in the frequency of FoxP3+ T cells with aging which, however, occurs within the CD4+CD25- T cells. Furthermore, whereas Tregs from young and old mice similarly suppress Teffs from young mice, both have a compromised suppressive capacity of Teffs from old mice, a phenomenon which is partially recovered in the presence of IL-2-producing CD4+CD62L+ non-Teffs. Finally, we observed that Teff subsets from old mice are enriched with IL-17A-producing T cells and exhibit intrinsically dysregulated expression of genes encoding cell-surface molecules and transcription factors, which play a key role in T-cell activation and regulation. We, thus, demonstrate an age-related impairment in the regulation of effector CD4 T cells, which may underlie the higher risk for destructive inflammation associated with aging.
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev , Beer Sheva , Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Harpaz
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev , Beer Sheva , Israel.
authors.forename: Udayan
authors.initials: U
authors.lastname: Bhattacharya
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev , Beer Sheva , Israel.
authors.forename: Yehezqel
authors.initials: Y
authors.lastname: Elyahu
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev , Beer Sheva , Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Strominger
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev , Beer Sheva , Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Monsonego
keywords: CD4 T cells; aging; inflammation; regulatory T cells; senescence