A common factor regulates both Th1‐ and Th2‐specific cytokine gene expression

• Published in: The EMBO journal 1994-02, Vol.13 (3), p.625-633
• Main Authors: Rooney, J.W., Hodge, M.R., McCaffrey, P.G., Rao, A., Glimcher, L.H.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Biological and medical sciences; CD3 Complex - immunology; Cell Line; Cloning, Molecular; Cyclosporine - metabolism; Cytokines - biosynthesis; Cytokines - genetics; DNA; DNA-Binding Proteins - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Interleukin-2 - genetics; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Ionomycin - pharmacology; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; NFATC Transcription Factors; Nuclear Proteins; Promoter Regions, Genetic; T-Lymphocytes, Helper-Inducer - metabolism; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1994.tb06300.x

Murine T helper cell clones are classified into two distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), on the basis of cytokine secretion patterns. Th1 clones produce interleukin‐2 (IL‐2), tumor necrosis factor‐beta (TNF‐beta) and interferon‐gamma (IFN‐gamma), while Th2 clones produce IL‐4, IL‐5, IL‐6 and IL‐10. These subsets differentially promote delayed‐type hypersensitivity or antibody responses, respectively. The nuclear factor NF‐AT is induced in Th1 clones stimulated through the T cell receptor‐CD3 complex, and is required for IL‐2 gene induction. The NF‐AT complex consists of two components: NF‐ATp, which pre‐exists in the cytosol and whose appearance in the nucleus is induced by an increase of intracellular calcium, and a nuclear AP‐1 component whose induction is dependent upon activation of protein kinase C (PKC). Here we report that the induction of the Th2‐specific IL‐4 gene in an activated Th2 clone involves an NF‐AT complex that consists only of NF‐ATp, and not the AP‐1 component. On the basis of binding experiments we show that this ‘AP‐1‐less’ NF‐AT complex is specific for the IL‐4 promoter and does not reflect the inability of activated Th2 cells to induce the AP‐1 component. We propose that NF‐ATp is a common regulatory factor for both Th1 and Th2 cytokine genes, and that the involvement of PKC‐dependent factors, such as AP‐1, may help determine Th1‐/Th2‐specific patterns of gene expression.