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Stimulation with PMA and ionomycin increased the frequencies of IL-10-producing CD4+ and CD8+ T cells in healthy controls and modestly in atopic nonasthmatics, but not in asthmatics. These results were surprising because we had expected that additional stimulus would enhance T cell IL-10 production in asthmatics, in whom the frequency of IL-10-producing T cells was increased at baseline. Although those compounds have been widely used to induce cytokine production from T cells in vitro, it does not seem to be the case with the induction of IL-10 in asthmatic subjects. An important caveat is that a full time course for the stimulation was not established, and time points later than 24 h may have given a greater response in asthmatics. However, at the 24 h time point, differences were noted between asthmatics and the other subjects. This raises the possibility that circulating T cells of asthmatic subjects are maximally stimulated with regard to IL-10 production; alternatively, IL-10 production T cells in asthmatics may be regulated differently than T cells in other subjects. A further possibility is that spontaneous production of IL-10 from T cells in vitro suppresses the PMA- or ionomycin-induced responses. Of note is a recent study that demonstrated that altering the balance between the protein kinase C pathway and calcium signalling redirected Th2 to Th1 and vice versa, although both signals were required for T cell activation , and stimulation for calcium signalling inhibited the production of IL-4, even in Th2 clones. Given that IL-10 has been regarded as a Th2-type cytokine and that atopic asthmatics are expected to have a Th2-skewed background, it is important to know whether a similar mechanism is involved for regulating IL-10 production.