Differential survival of cytotoxic T cells and memory cell precursors.
It is widely assumed that the development of memory CD8 T cells requires the escape of CTLs from programmed cell death. We show in this study that although serine protease inhibitor 6 (Spi6) is required to protect clonal bursts of CTLs from granzyme B-induced programmed cell death, it is not required for the development of memory cells. This conclusion is reached because memory cell precursors down-regulate both Spi6 and granzyme B, unlike CTLs, and they do not require Spi6 for survival. These findings suggest that memory CD8 T cells are derived from progenitors that are refractory to self-inflicted damage, rather than derived from fully differentiated CTLs.
Zhang
Manling
M
Department of Pathology, Ben May Institute for Cancer Research and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Byrne
Susan
S
Liu
Ni
N
Wang
Yue
Y
Oxenius
Annette
A
Ashton-Rickardt
Philip G
PG
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D015843:Serpins / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*
D008565:Membrane Proteins; D015843:Serpins; D053804:Granzymes; D012697:Serine Endopeptidases; C106610:Serpinb9 protein, mouse