[Chronic hypereosinophilia: a model of Th2 disorders].
Interleukin-5 produced by Th2-type lymphocytes is involved in the pathogenesis of a number of hypereosinophilic disorders. We and others have identified clonal Th2 cells with abnormal surface phenotypes in peripheral blood of certain patients presenting the idiopathic hypereosinophilic syndrome. We took advantage of the CD3- CD4+ phenotype of our patients' T cells to determine the activation signals involved in their production of Th2 cytokines and expansion, independently of T cell receptor engagement. In vitro cocultures performed with dendritic cells demonstrated the critical role of co-stimulatory signalling through B.7/CD28 and LFA-3/CD2 pathways and the involvement of an autocrine IL2/IL2R loop in the activation of these Th2-type cells. The high-level spontaneous apoptosis displayed by these cells in vitro was drastically inhibited by IL2 and IFN-alpha. New therapeutic strategies could result from our observations. Indeed, the hypereosinophilic syndrome may represent an unexpected application of new immunomodulatory molecules such as CTLA4-Ig and anti-IL2R-alpha.
Roufosse
F
F
Service d'immunologie-hématologie-transfusion, Hôpital Erasme, Université libre de Bruxelles, Belgique.
Schandené
L
L
Cogan
E
E
Goldman
M
M
D017209:Apoptosis; D003713:Dendritic Cells; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000276:immunology / Q000503:physiopathology*; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D016898:Interferon-alpha; D007376:Interleukin-2