Interferon a prevents spontaneous apoptosis of clonal Th2 cells associated with chronic hypereosinophilia

A recent study identified a clonal expansion of CD32CD41cells secreting Th2-type cytokines in 4 patients with chronic hypereosinophilia. Because interferon a (IFN-a) is used in the therapy of the idiopathic hypereosinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined. First, these cells displayed a high rate of spontaneous apoptosis on culture in cytokine-free medium and were also sensitive to Fas-mediated apoptosis induced by soluble Fas ligand. Addition of IFN-a or interleukin-2 (IL-2) to culture medium resulted in significant protection against spontaneous but not Fas-induced apoptosis. Although spontaneous apoptosis of the clonal Th2 cells was clearly associated with downregulation of both bcl-2 and bcl-xL levels, IFN-a had no significant effect on the expressionof theseantiapoptoticproteins,whereas addition of IL-2 resulted in higher levels of bcl-2. On the other hand, IFN-a decreased the numbers of cells with disrupted mitochondrial transmembranepotentialbothduring spontaneous apoptosis and after exposure to protoporphyrin IX. Thus, IFN-a might promote the survival of clonal Th2 cells, an effect that could be relevant to the therapeutic approach for patients with chronic hypereosinophilia caused by clonal expansion of Th2-type cells. (Blood. 2000;96:4285-4292)