Serine protease inhibitor 2A is a protective factor for memory T cell development

Nat Immunol. 2004 Sep;5(9):919-26. doi: 10.1038/ni1107. Epub 2004 Aug 15.


An essential event in the development of memory CD8(+) T lymphocytes is the escape of progenitors from programmed cell death, but how this is mediated is unclear. Here we report that the gene encoding serine protease inhibitor 2A (Spi2A), an inhibitor of lysosomal executioner proteases dependent on transcription factor NF-kappaB, is upregulated in memory cell precursors. Spi2A upregulation protected lymphocytic choriomeningitis virus-specific memory progenitors from programmed cell death. Thus, Spi2A promotes the survival of cytotoxic T lymphocytes, allowing them to differentiate into memory CD8 T cells. These findings suggest a model in which commitment to the memory lineage is facilitated by the upregulation of protective genes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Granulocyte Precursor Cells / immunology*
  • Humans
  • Immunologic Memory*
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Nuclear Proteins / immunology*
  • Oligonucleotide Array Sequence Analysis
  • Radiation Chimera
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serpins*
  • Up-Regulation


  • Nuclear Proteins
  • Serpina3k protein, mouse
  • Serpins