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

A recent study identified a clonal expansion of CD3-CD4(+) cells secreting Th2-type cytokines in 4 patients with chronic hypereosinophilia. Because in terferon alpha (IFN-alpha) is used in the therapy of the idiopathic hypereo sinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined. First, th ese cells displayed a high rate of spontaneous apoptosis on culture in cyto kine-free medium and were also sensitive to Fas mediated apoptosis induced by soluble Fas ligand, Addition of IFN-alpha or interleukin4 (IL-2) to cult ure medium resulted in significant protection against spontaneous but not F as-induced apoptosis, Although spontaneous apoptosis of the clonal Th2 cell s was clearly associated with downregulation of both bcl-2 and bcl-x(L) lev els, IFN-alpha had no significant effect on the expression of these antiapo ptotic proteins, whereas addition of IL-2 resulted in higher levels of bcl- 2. On the other hand, IFN-alpha decreased the numbers of cells with disrupt ed mitochondrial transmembrane potential both during spontaneous apoptosis and after exposure to protoporphyrin IX. Thus, IFN-alpha might promote the survival of clonal Th2 cells, an effect that could be relevant to the thera peutic approach for patients with chronic hypereosinophilia caused by clona l expansion of Th2-type cells, (C) 2000 by The American Society of Hematolo gy.