Therefore, it is possible that the strong induction of immune activation in these foods requires the combination of high-molecular weight phenolic compounds and b-glucan. It will be important to Publications Using Abomle FK506 investigate this relationship as well as the other possible relationships in the future. In mice, the CD4 molecule is well known as a primary receptor expressed not only on the T-helper cells but also bone marrow myeloid and splenic dendritic cells. Moreover, it has been reported that CD4 in human monocytes acts as a signalling molecule for the induction of calcium flux and for the activation of protein kinase C. We demonstrated here that polymerised phenylpropanoic acids Abmole GSK1120212 induced IFN-c and GM-CSF production from murine splenocytes, and that the T cell population and the CD4 molecule are important for the induction of cytokine activity. Several polyphenols have been reported to bind to CD4 molecules. For instance, EGCG has demonstrated anti-HIV activity through binding to CD4 and interfering with gp120 binding. In addition, part of the antiHIV activity of lignins was shown by inhibition of CD4, which is involved in the entry of HIV into the cells. Our results here show that polymerised phenylpropanoic acids bind directly to the CD4 molecule and the specificity of this binding was suggested by the result that polymerised polyphenols did not bind to the CD8a and CD3e molecule. High-molecularweight polyphenols could induce the polymerisation of CD4 molecules on a limited area of cell surface and lead to subsequent cell�Ccell interaction, resulting in the activation of the immune system. In addition, the immune activation induced by polymerised polyphenols might be mediated by T cell-dependent and T cell-independent mechanisms, because the IFN-c and GM-CSF production induced by polymerised polyphenols was observed even in the absence of T cells from splenocytes. Thus, further investigation is needed to reveal the mechanisms of polymerised polyphenols and IFN-c and GM-CSF, as well as to identify the cells secreting cytokines. In addition, it is important to determine whether enzymatically polymerised polyphenols are responsible for cytokine induction, and have potential for use in immunological applications. In conclusion, this study indicates that the polymerised polyphenols synthesised by enzymes, but not monomers, strongly induce cytokine production from murine splenocytes. These results are important, and therefore, further work is required to elucidate the intricacies of these immunomodulating effects exhibited by polymerised polyphenols. Our findings contribute to understanding the mechanisms by which foods induce immunomodulating activity.