A CONSERVED MOTIF IN THE PROMOTERS OF SEVERAL CYTOKINES EXPRESSED BY HUMAN TH2-TYPE LYMPHOCYTES

We have recently found a novel conserved motif in the promoters of sev eral T-cell-expressed cytokines [human interleukin-2, -4, -5 and -13 a nd human and mouse granulocyte/macrophage- colony stimulating factor ( GM-CSF)]. It contains a core sequence CTTGG...CCAAG which is present a s part of larger palindromic sequences in each gene. This suggests tha t they may interact with a new family of trans-acting factors. In tran sfection assays, the human GM-CSF element has a strong positive effect on the expression of a reporter gene by the human T cell line Jurkat J6 upon stimulation. In DNA mobility shift assays, this sequence can g ive either six different specific bands which are competed out by diff erent parts of the sequence or one specific band which is competed out by each of the inverted repeats, depending on the reconstitution cond itions. In different genes, the core sequences are separated by intege r numbers of helical turns. Considering the strong positive regulatory effect of this element and its presence in several T-cell-expressed c ytokine genes, it may be crucial to the coordinated expression of thes e cytokines in T helper cells.