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Protective function and durability of mouse lymph node-resident memory CD8+ T cells.

Scott M Anthony1, Natalija Van Braeckel-Budimir1, Steven J Moioffer1

  • 1Department of Pathology, The University of Iowa, Iowa City, United States.

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|June 18, 2021
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Summary

Repeated influenza A virus (IAV) infections generate quaternary memory (4M) CD8+ T cells. These 4M CD8+ T cells provide superior protection against viral infection by forming durable tissue-resident memory (Trm) populations.

Keywords:
CD8+ T cellCD8+ T cell resident memoryimmunologyinflammationlunglymph nodemouserepeated antigen exposurevirus infection

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Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Tissue-resident memory CD8+ T cells (Trm) are crucial for protective immunity against respiratory viruses like influenza A virus (IAV).
  • The formation and durability of Trm populations following IAV infection are not fully understood, particularly concerning the impact of repeated exposures.

Purpose of the Study:

  • To investigate the characteristics and protective capacity of memory CD8+ T cell populations generated after repeated IAV infections.
  • To compare the efficacy of primary memory (1M) versus quaternary memory (4M) CD8+ T cells in controlling viral infections.

Main Methods:

  • Induction of primary and quaternary memory CD8+ T cell populations in mice through controlled IAV infection and re-exposure.
  • Flow cytometry analysis to identify and quantify CD69+CD103+ Trm populations in mediastinal lymph nodes (mLNs) and lung tissue.
  • Assessment of granzyme A/B expression and gene expression profiling of memory CD8+ T cells.

Main Results:

  • Repeated IAV infections generate quaternary memory (4M) CD8+ T cells in mLNs, distinct from primary memory (1M) populations.
  • 4M CD8+ T cells exhibit enhanced protection against viral infection in mLNs compared to 1M CD8+ T cells.
  • Stable maintenance of CD69+CD103+ 4M CD8+ Trm cells in mLNs and lungs, contrasting with the decline of 1M CD8+ Trm cells, is associated with enhanced granzyme A/B expression.

Conclusions:

  • Repeated antigen exposure, mimicking seasonal influenza, enhances the capacity of circulating memory CD8+ T cells to form long-lived Trm populations.
  • These enhanced Trm populations, particularly 4M CD8+ T cells, improve control of viral infections in the mediastinal lymph nodes.