Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4+ T cells.
In contrast to naïve CD4+ T cells, memory CD4+ T cells rapidly express high levels of effector cytokines in response to antigen stimulation. The molecular mechanism for this specific behavior is not well understood. The nuclear factor of activated T cells (NFAT) family of transcription factors plays an important role in the transcription of many cytokine genes. Here we show that memory CD4+ T cells rapidly induce NFAT-mediated transcription upon T cell receptor ligation whereas NFAT activation in naïve CD4+ T cells requires longer periods of stimulation. The difference in kinetics correlates with the low levels of NFATc1 and NFATc2 proteins present in naïve CD4+ T cells and their high levels in memory CD4+ T cells. Accordingly, IL-2 expression requires NFAT activation only in memory CD4+ T cells whereas it is NFAT-independent in naïve CD4+ T cells. Thus, the accumulation of NFATc1 and NFATc2 in memory CD4+ T cells represents a previously uncharacterized regulatory mechanism for the induction of early gene expression after antigen stimulation.
Dienz
Oliver
O
Department of Medicine/Immunobiology Program, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA.
Eaton
Sheri M
SM
Krahl
Troy J
TJ
Diehl
Sean
S
Charland
Colette
C
Dodge
John
J
Swain
Susan L
SL
Budd
Ralph C
RC
Haynes
Laura
L
Rincon
Mercedes
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation; D007156:Immunologic Memory / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D000939:Epitopes; D007376:Interleukin-2; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D012333:RNA, Messenger