DOWN-REGULATION OF IL-4 GENE-TRANSCRIPTION AND CONTROL OF TH2 CELL-DIFFERENTIATION BY A MECHANISM INVOLVING NFAT1

Transcription factors of the NFAT family play a critical role in the i mmune response by activating the expression of cytokines and other ind ucible genes in antigen-stimulated cells. Here we show that a member o f this family, NFAT1, is involved in down-regulating the late phase of IL-4 gene transcription, thus inhibiting T helper 2 responses. Wherea s stimulated T cells from wild-type mice show a transient increase and then a rapid decline in the steady-state levels of IL-4 mRNA in vitro , the levels of IL-4 gene transcripts in NFAT1-deficient T cells are m aintained at high levels under the same conditions. Consistent with th is observation, NFAT1(-/-) mice are more susceptible to infection with Leishmania major. This report provides evidence that NFAT proteins re gulate not only the initiation but also the termination of gene transc ription.