Abstract：
:On activation, umbilical cord blood (UCB) CD4(+) T cells demonstrate reduced expression of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), whereas maintaining equivalent interleukin-2 (IL-2) levels, as compared with adult peripheral blood (PB) CD4(+) T cells. Nuclear factor of activated T cells (NFAT1) protein, a transcription factor known to regulate the expression of IL-2, TNF-alpha and IFN-gamma, is reduced in resting and activated UCB CD4(+) T cells. In contrast, expression of Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar homology 1 bZip transcription factor 2 (BACH2) was shown by gene array analyses to be increased in UCB CD4(+) T cells and was validated by qRT-PCR. Using chromatin immunoprecipitation, BACH2 was shown binding to the human IL-2 proximal promoter. Knockdown experiments of BACH2 by transient transfection of UCB CD4(+) T cells with BACH2 siRNA resulted in significant reductions in stimulated IL-2 production. Decreased IL-2 gene transcription in UCB CD4(+) T cells transfected with BACH2 siRNA was confirmed by a human IL-2 luciferase assay. In summary, BACH2 maintains IL-2 expression in UCB CD4(+) T cells at levels equivalent to adult PB CD4(+) T cells despite reduced NFAT1 protein expression. Thus, BACH2 expression is necessary to maintain IL-2 production when NFAT1 protein is reduced, potentially impacting UCB graft CD4(+) T-cell allogeneic responses.
journal_name
Leukemiajournal_title
Leukemiaauthors
Lesniewski ML,Haviernik P,Weitzel RP,Kadereit S,Kozik MM,Fanning LR,Yang YC,Hegerfeldt Y,Finney MR,Ratajczak MZ,Greco N,Paul P,Maciejewski J,Laughlin MJdoi
10.1038/leu.2008.234subject
Has Abstractpub_date
2008-12-01 00:00:00pages
2201-7issue
12eissn
0887-6924issn
1476-5551pii
leu2008234journal_volume
22pub_type
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