Regulatory T cells limit unconventional memory to preserve the capacity to mount protective CD8 memory responses to pathogens

Proc Natl Acad Sci U S A. 2019 May 14;116(20):9969-9978. doi: 10.1073/pnas.1818327116. Epub 2019 Apr 29.

Abstract

Immunological memory exists so that following infection an expanded population of pathogen-specific lymphocytes can rapidly and efficiently control infection in the case of reexposure. However, in the case of CD8+ T lymphocytes, a population of unconventional CD44+CD122+ virtual memory T cells (TVM) has been described that possesses many, though not all, features of "true memory" T cells, without the requirement of first encountering cognate antigen. Here, we demonstrate a role for regulatory T cell-mediated restraint of TVM at least in part through limiting IL-15 trans-presentation by CD11b+ dendritic cells. Further, we show that keeping TVM in check ensures development of functional, antigen-specific "true" memory phenotype CD8+ T cells that can assist in pathogen control upon reexposure.

Keywords: IL-15; regulatory T cells; unconventional memory T cells; virtual memory T cells; virus infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / physiology
  • CTLA-4 Antigen / physiology
  • Dendritic Cells / physiology
  • Immunologic Memory*
  • Integrin beta1
  • Interleukin-15 / physiology
  • Male
  • Mice
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • CTLA-4 Antigen
  • Integrin beta1
  • Interleukin-15