Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2

Nat Commun. 2014 Nov 5:5:5377. doi: 10.1038/ncomms6377.

Abstract

It is unclear how CD4 T-cell memory formation is regulated following pathogen challenge, and when critical mechanisms act to determine effector T-cell fate. Here, we report that following influenza infection most effectors require signals from major histocompatibility complex class II molecules and CD70 during a late window well after initial priming to become memory. During this timeframe, effector cells must produce IL-2 or be exposed to high levels of paracrine or exogenously added IL-2 to survive an otherwise rapid default contraction phase. Late IL-2 promotes survival through acute downregulation of apoptotic pathways in effector T cells and by permanently upregulating their IL-7 receptor expression, enabling IL-7 to sustain them as memory T cells. This new paradigm defines a late checkpoint during the effector phase at which cognate interactions direct CD4 T-cell memory generation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autocrine Communication
  • CD27 Ligand / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Genes, MHC Class II
  • Immunologic Memory*
  • Influenza A virus / immunology*
  • Interleukin-2 / metabolism*
  • Interleukin-7 / metabolism*
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • CD27 Ligand
  • CD70 protein, human
  • Interleukin-2
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • interleukin-7, mouse

Associated data

  • GEO/GSE60186