The CD4⁺ T-cell help signal is transmitted from APC to CD8⁺ T-cells via CD27-CD70 interactions

Nat Commun. 2012 Jul 10;3:948. doi: 10.1038/ncomms1948.


CD8(+) cytotoxic T lymphocytes are critical components of immunity against infectious pathogens, tumours, and in the case of pathogenic autoimmunity, normal self tissues. CD4(+) T (T(H)) cells provide 'help' to CD8(+) cytotoxic T lymphocytes during priming by first activating antigen-presenting cells via CD40-CD40L interactions. Here we show that, after immunization with either a noninflammatory, nonreplicating antigen or an overtly inflammatory replicating antigen, CD8(+) cytotoxic T lymphocytes prevented from receiving a signal through CD27 during priming subsequently exhibit a specific defect in their capacity for secondary expansion that can be rescued by the absence of TRAIL. Thus, the 'help message' is transmitted to CD8(+) T cells via CD70-CD27 signals, enabling them to undergo secondary expansion and avoid TRAIL-mediated apoptosis on re-stimulation. These findings complete our understanding of the cellular interactions through which T(H) is provided to CD8(+) cytotoxic T lymphocytes during priming.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism*
  • CD27 Ligand / genetics
  • CD27 Ligand / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Flow Cytometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*


  • CD27 Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • CD40 Ligand