IFN-gamma production from human Th1 cells is controlled by Raf kinase

Raf kinase is an important intracellular mediator in T cell signalling and may be crucial for the proliferation of this inflammatory cell. In order to elucidate its effect on cytokine production by human T cells in response to T cell receptor activation, experiments were carried out on human T cell clones using antisense (AS) oligodeoxynucleotides (ODN) to inhibit the expression of Raf kinase. AS ODN to Raf were shown to have a significant effect on a human Th1-like T cell clone, inhibiting antiCD3-induced IFN-gamma secretion by 76%, whereas no inhibitory effect was observed on IL-5 or IL-4 production by a Th2-like clone. IL-2 secretion from both clones was also not affected by the Raf AS ODN. In all cases, a reduction in Raf kinase within the cell was demonstrated by Western blot. Our results clearly demonstrate the importance of Raf kinase in the production of IFN-gamma from Th1 cells, but also show the lack of effect of this intracellular mediator on cytokine (IL-5, IL-4) release from Th2 cells.