Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4⁺ T cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-04, Vol.104 (17), p.7175-7180
• Main Authors: Dienz, Oliver, Eaton, Sheri M, Krahl, Troy J, Diehl, Sean, Charland, Colette, Dodge, John, Swain, Susan L, Budd, Ralph C, Haynes, Laura, Rincon, Mercedes
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation; Epitopes - immunology; Gene Expression Regulation; Immunologic Memory - immunology; Interleukin-2 - biosynthesis; Interleukin-2 - metabolism; Mice; NFATC Transcription Factors - antagonists & inhibitors; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcriptional Activation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0610442104

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.