Blood-Derived CD4 T Cells Naturally Resist Pyroptosis during Abortive HIV-1 Infection

Cell Host Microbe. 2015 Oct 14;18(4):463-70. doi: 10.1016/j.chom.2015.09.010.


Progression to AIDS is driven by CD4 T cell depletion, mostly involving pyroptosis elicited by abortive HIV infection of CD4 T cells in lymphoid tissues. Inefficient reverse transcription in these cells leads to cytoplasmic accumulation of viral DNAs that are detected by the DNA sensor IFI16, resulting in inflammasome assembly, caspase-1 activation, and pyroptosis. Unexpectedly, we found that peripheral blood-derived CD4 T cells naturally resist pyroptosis. This resistance is partly due to their deeper resting state, resulting in fewer HIV-1 reverse transcripts and lower IFI16 expression. However, when co-cultured with lymphoid-derived cells, blood-derived CD4 T cells become sensitized to pyroptosis, likely recapitulating interactions occurring within lymphoid tissues. Sensitization correlates with higher levels of activated NF-κB, IFI16 expression, and reverse transcription. Blood-derived lymphocytes purified from co-cultures lose sensitivity to pyroptosis. These differences highlight how the lymphoid tissue microenvironment encountered by trafficking CD4 T lymphocytes dynamically shapes their biological response to HIV.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology*
  • Cells, Cultured
  • Coculture Techniques
  • Gene Expression
  • HIV-1 / growth & development*
  • Humans
  • NF-kappa B / biosynthesis
  • Nuclear Proteins / biosynthesis
  • Phosphoproteins / biosynthesis
  • Pyroptosis*
  • Real-Time Polymerase Chain Reaction


  • NF-kappa B
  • Nuclear Proteins
  • Phosphoproteins
  • IFI16 protein, human