A critical role for NF-kappaB transcription factors in the development of CD8+ memory-phenotype T cells.
Memory T cells are essential for generating secondary immune responses and so provide long-lived protection from pathogens. The mechanisms that regulate the differentiation and survival of memory T cells are largely unknown. Transgenic mice in which NF-kappaB activity is inhibited by the expression of a dominant-negative form of IkappaB-alpha (mIkappaB-alpha mice) have drastically diminished numbers of CD8(+) memory-phenotype cells. The development of activated mIkappaB-alpha CD8 cells into memory-phenotype CD8 cells was severely impaired after adoptive transfer to lymphopenic hosts. Our findings demonstrate a critical role for NF-kappaB transcription factors in determining the number of memory-phenotype CD8 cells.
Hettmann
Thore
T
The Laboratory of Cardiovascular Biology, Harvard School of Public Health and Harvard Medical School, Boston, MA 02115, USA.
Opferman
Joseph T
JT
Leiden
Jeffrey M
JM
Ashton-Rickardt
Philip G
PG
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology*; D005434:Flow Cytometry; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha