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Changes in Natural Killer Cells in Aged Mice

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  • First Online:
Handbook of Immunosenescence

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Abstract

Immune dysfunctions in the elderly result in increased susceptibility to infectious diseases, cancer, or autoimmune diseases. Natural killer (NK) cells are bone marrow derived lymphocytes crucial for host defense against several infections and cancer. It is known that aged C57BL/6 mice compared to young mice have decreased numbers of mature NK cells in the blood, spleen, and bone marrow, resulting in susceptibility to mousepox, a lethal disease caused by Ectromelia virus. The chapter discusses newly described age-related defects in NK cells including reduced proliferation in vivo, dysregulated expression of activating and inhibitory receptors, and altered expression of collagen binding integrins. The chapter also describes that the defect in NK maturation is the consequence of deficient maturational cues provided by bone marrow stromal cells. Treatment with complexes of the cytokine IL-15 and IL-15Rα induce massive expansion of the NK cells but most of these NK cells remain immature and are unable to restore resistance to mousepox. Therefore, it may be crucial to design therapies that specifically increase mature NK cell numbers in the aged.

Some parts of this chapter were previously published in Nair S, Fang M, Sigal LJ. The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL-15/IL-15Ralpha treatment. Aging Cell. 2015;14(2):180–90. https://doi.org/10.1111/acel.12291. PubMed PMID: 25399821.

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Author information

Authors and Affiliations

  1. Immuno-Oncology Infection & Immunity Translational Research Science Communications Competitive Intelligence, Philiadelphia, PA, USA

    Savita Nair

  2. Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA

    Luis J. Sigal

Authors
  1. Savita Nair
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  2. Luis J. Sigal
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Correspondence to Luis J. Sigal .

Editor information

Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, QC, Canada

    Tamas Fulop

  2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

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Nair, S., Sigal, L.J. (2019). Changes in Natural Killer Cells in Aged Mice. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_97-1

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  • DOI: https://doi.org/10.1007/978-3-319-64597-1_97-1

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  • Print ISBN: 978-3-319-64597-1

  • Online ISBN: 978-3-319-64597-1

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