A COMMON FACTOR REGULATES BOTH TH1-SPECIFIC AND TH2-SPECIFIC CYTOKINE GENE-EXPRESSION

被引:155
作者
ROONEY, JW
HODGE, MR
MCCAFFREY, PG
RAO, A
GLIMCHER, LH
机构
[1] HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115
[3] HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115
[4] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115
[5] HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115
关键词
INTERLEUKIN-2; INTERLEUKIN-4; T-CELL ACTIVATION; T-HELPER-1 AND T-HELPER-2 CELLS; TRANSCRIPTION;
D O I
10.1002/j.1460-2075.1994.tb06300.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:625 / 633
页数:9
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