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 interferon alpha (IFN-alpha) 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-alpha 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 down-regulation of both bcl-2 and bcl-x(L) levels, IFN-alpha had no significant effect on the expression of these antiapoptotic 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 disrupted 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 therapeutic approach for patients with chronic hypereosinophilia caused by clonal expansion of Th2-type cells. (Blood. 2000;96:4285-4292)
Schandené
L
L
Department of Immunology, Hôpital Erasme, Brussels, Belgium.
Roufosse
F
F
de Lavareille
A
A
Stordeur
P
P
Efira
A
A
Kennès
B
B
Cogan
E
E
Goldman
M
M
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002908:Chronic Disease; D002999:Clone Cells / Q000187:drug effects; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011524:Protoporphyrins / Q000494:pharmacology; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects*; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology
C494811:BCL2L1 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D051020:bcl-X Protein; D019014:fas Receptor; D013481:Superoxides; C028025:protoporphyrin IX