Making sense of inflammation, epigenetics, and memory CD8+ T-cell differentiation in the context of infection

Authors

  • Erika L. Pearce,

    1. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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  • Hao Shen

    Corresponding author
    1. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
      Hao Shen
      Department of Microbiology
      University of Pennsylvania School of Medicine
      3610 Hamilton Walk
      302D Johnson Pavilion
      Philadelphia, PA 19104
      USA
      Tel.: +1 215 573 5259
      Fax: +1 215 573 2890
      E-mail: hshen@mail.med.upenn.edu
    Search for more papers by this author

Hao Shen
Department of Microbiology
University of Pennsylvania School of Medicine
3610 Hamilton Walk
302D Johnson Pavilion
Philadelphia, PA 19104
USA
Tel.: +1 215 573 5259
Fax: +1 215 573 2890
E-mail: hshen@mail.med.upenn.edu

Abstract

Summary:  Recent findings suggest a new paradigm that early inflammatory cytokines promote the effector T-cell response while inhibiting the development of CD8+ T-cell memory. Although this opposing effect may appear paradoxical at first, it makes biological sense in the context of an infection, by ensuring a maximal effector response that will clear the pathogen. Once infection is controlled, the withdrawal of inflammatory cytokines allows the differentiation of effectors into long-lived memory cells that provide protective immunity against re-infection. Memory T cells differ from naïve T cells in their responsiveness to stimulation, which leads to the rapid expression of effector functions. The molecular basis for enhanced functionality of memory T cells remains largely unknown. Recent results indicate that certain epigenetic changes are imprinted in memory T cells that play an important role in keeping them poised to respond immediately upon antigen re-encounter. These epigenetic modifications occur as naïve T cells become activated and are influenced by factors that regulate memory formation. Thus, epigenetic changes are an integral component of memory T-cell differentiation, while inflammation plays an unexpected regulatory role in the process. These advances in our understanding of T-cell memory will undoubtedly help design unconventional vaccine strategies for inducing large populations of long-lived and functional memory CD8+ T cells.

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