Non-malignant clonal expansions of CD8+ memory T cells in aged individuals

Authors

  • Eric T. Clambey,

    1. Integrated Department of Immunology, National Jewish Research & Medical Center, Denver, CO, USA.
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  • Linda F. Van Dyk,

    1. Integrated Department of Immunology, National Jewish Research & Medical Center, Denver, CO, USA.
    2. Department of Microbiology, University of Colorado Health Sciences Center at Fitzsimmons, Aurora, CO, USA.
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  • John W. Kappler,

    1. Integrated Department of Immunology, National Jewish Research & Medical Center, Denver, CO, USA.
    2. Howard Hughes Medical Institute, National Jewish Research & Medical Center, Denver, CO, USA.
    3. Department of Medicine, University of Colorado Health Sciences Center at Fitzsimmons, Aurora, CO, USA.
    4. Department of Pharmacology, University of Colorado Health Sciences Center at Fitzsimmons, Aurora, CO, USA.
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  • Philippa Marrack

    Corresponding author
    1. Integrated Department of Immunology, National Jewish Research & Medical Center, Denver, CO, USA.
    2. Howard Hughes Medical Institute, National Jewish Research & Medical Center, Denver, CO, USA.
    3. Department of Medicine, University of Colorado Health Sciences Center at Fitzsimmons, Aurora, CO, USA.
    4. Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center at Fitzsimmons, Aurora, CO, USA.
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* Philippa Marrack
National Jewish Research & Medical Center
Integrated Department of Immunology
Goodman Building, 5th Floor, 1400 Jackson Street
Denver, CO 80206
USA
Tel.: +1303 398 1322
Fax: +1303 398 1396
E-mail: marrackp@njc.org

Abstract

Summary:  CD8+ T cells provide a major line of defense against intracellular pathogens. Upon encounter with antigen, CD8+ T cells go through three distinct phases involving proliferation, contraction, and differentiation to become eventually long-lived CD8+ memory T cells. CD8+ memory T cells provide long-term protection against infection by intracellular pathogens. CD8+ memory T-cell proliferation and survival are regulated by many factors, including cytokines, and CD8+ memory T cells are stably maintained over a period of months to years. In aged humans and mice, however, there are significant alterations to the CD8+ memory T-cell compartment with frequent development of monoclonal expansions of CD8+ memory T cells in healthy individuals. Interestingly, CD8+ clonal expansions are not malignant and do not progress to lymphomas, suggesting that these cells must still be under certain constraints. In this review, we discuss our current understanding of factors that contribute to and regulate these CD8+ clonal expansions as well as the impact of CD8+ clonal expansions on immune function of the aged. In addition, we discuss similarities and differences between CD8+ clonal expansions observed in humans and mice, and we postulate that CD8+ clonal expansions represent a spectrum of biological outcomes ranging from antigen-driven to antigen-independent phenomena.

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