Serine protease inhibitor 2A is a protective factor for memory T cell development.
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.
Committees on Immunology and Developmental Biology, Department of Pathology, Ben May Institute for Cancer Research and Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, 924 East 57th Street, Chicago, Illinois 60637, USA.
Ni
N
Liu
Tiphanie
T
Phillips
Manling
M
Zhang
Yue
Y
Wang
Joseph T
JT
Opferman
Ramila
R
Shah
Philip G
PG
Ashton-Rickardt
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D042381:Granulocyte Precursor Cells / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D011828:Radiation Chimera; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins; D015854:Up-Regulation
D009687:Nuclear Proteins; C490400:Serpina3k protein, mouse; D015843:Serpins