T cell clonality in patients with idiopathic hypereosinophilic syndrome: prognostic and therapeutic implications

Interleukin-5 produced by Th2 lymphocytes is involved in the pathogenesis o f a number of hypereosinophilic disorders. We and others have identified ph enotypically abnormal clonal Th2 cells in peripheral blood of certain patie nts presenting the idiopathic hypereosinophilic syndrome (IHS). The premali gnant nature of the aberrant lymphocytes is suggested by the occasional dev elopment of a peripheral T cell lymphoma bearing the same phenotype. In our series of five patients, the T cell clones all bore a CD3- CD4+ phenotype. The production of type-2 cytokines and the proliferation of these cells in response to dendritic cells in vitro were dependent on engagement of CD2 a nd CD28 molecules and on an IL-2/IL-2R autocrine loop. The high-level spont aneous apoptosis displayed by these cells in vitro was drastically inhibite d by IL-2 and IFN-alpha, suggesting that administration of IFN-alpha to suc h patients could favour further expansion and eventual malignant transforma tion of the T cell clone. The hypereosinophilic syndrome may represent an u nexpected application of new immunomodulatory molecules such as CTLA4-lg an d anti-IL-2R-alpha. (C) 2001 Editions scientifiques et medicales Elsevier S AS.