Deficient IFN-gamma expression in umbilical cord blood (UCB) T cells can be rescued by IFN-gamma-mediated increase in NFATc2 expression.
Regulation of nuclear factor of activated T cells-c2 (NFATc2) gene expression is not clearly defined. We previously reported reduced NFATc2 protein expression in cord blood T lymphocytes. Here we show that NFATc2 expression in T cells is dependent in part on the presence of IFN-gamma during primary stimulation, as blocking of IFN-gamma blunted NFATc2 protein and mRNA upregulation. Conversely, addition of exogenous IFN-gamma during stimulation resulted in increased expression of NFATc2 in cord blood T lymphocytes. This correlated with rescue of deficient IFN-gamma expression by cord blood T cells. Rescue of IFN-gamma expression in cord blood T cells was dependent on the presence of antigen-presenting cells, as addition of IFN-gamma during stimulation of purified cord blood T cells did not result in an increase of IFN-gamma expression, and depletion of monocytes ablated the rescue of IFN-gamma expression. Our results point to impaired function in the antigen-presenting cell population of cord blood, playing a role in the hyporesponsiveness of T cells.
Kadereit
Suzanne
S
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-5061, USA. sxk79@po.cwru.edu
Junge
Gwendolyn R
GR
Kleen
Thomas
T
Kozik
Margaret M
MM
Kaminski
Beth A
BA
Daum-Woods
Kathleen
K
Fu
Pingfu
P
Tary-Lehmann
Magdalena
M
Laughlin
Mary J
MJ
D003208:Concanavalin A / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D003208:Concanavalin A; D007371:Interferon-gamma