PLoS Pathogens (May 2019)

Early primed KLRG1- CMV-specific T cells determine the size of the inflationary T cell pool.

  • Nicolas S Baumann,
  • Suzanne P M Welten,
  • Nicole Torti,
  • Katharina Pallmer,
  • Mariana Borsa,
  • Isabel Barnstorf,
  • Jennifer D Oduro,
  • Luka Cicin-Sain,
  • Annette Oxenius

DOI
https://doi.org/10.1371/journal.ppat.1007785
Journal volume & issue
Vol. 15, no. 5
p. e1007785

Abstract

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Memory T cell inflation is a process in which a subset of cytomegalovirus (CMV) specific CD8 T cells continuously expands mainly during latent infection and establishes a large and stable population of effector memory cells in peripheral tissues. Here we set out to identify in vivo parameters that promote and limit CD8 T cell inflation in the context of MCMV infection. We found that the inflationary T cell pool comprised mainly high avidity CD8 T cells, outcompeting lower avidity CD8 T cells. Furthermore, the size of the inflationary T cell pool was not restricted by the availability of specific tissue niches, but it was directly related to the number of virus-specific CD8 T cells that were activated during priming. In particular, the amount of early-primed KLRG1- cells and the number of inflationary cells with a central memory phenotype were a critical determinant for the overall magnitude of the inflationary T cell pool. Inflationary memory CD8 T cells provided protection from a Vaccinia virus challenge and this protection directly correlated with the size of the inflationary memory T cell pool in peripheral tissues. These results highlight the remarkable protective potential of inflationary CD8 T cells that can be harnessed for CMV-based T cell vaccine approaches.