Springer Online Journal Archives 1860-2000
Abstract Background: Even though the presence of a prominent tissue eosinophiliarepresents a common histopathologic feature of Hodgkin's disease (HD),eosinophils have been mainly regarded as ‘innocent’ bystanders recruited andactivated during the cellular reaction typical of HD. To evaluate theputative role of eosinophils or eosinophil-derived cytokines on tumor-cellregulation in HD, we have analyzed these cells for the functional expressionof surface ligands (L) of the tumor necrosis factor (TNF) superfamily, whosespecific receptors are known to transduce proliferation signals at thesurface of Hodgkin (H) and Reed–;Sternberg (RS) cells. Materials and methods: Eosinophils from peripheral blood of healthydonors and patients with HD, primary hypereosinophilic syndrome (HES), orsecondary hypereosinophilia (HE), were purified by density gradientcentrifugation and immunomagnetic depletion of residual granulocytes. Results: By immunostaining and mRNA analysis, we were able to show thateosinophils from normal donors and patients with HD, HES, and HE express anumber of receptors and ligands of the TNF superfamily, including CD40,CD40L, CD30L, CD95/Fas, CD95/FasL and 4-1BB. In addition, we provideevidence that cytokines regulating eosinophil proliferation and activation,i.e., interleukin (IL)-5, IL-3, and granulocyte-macrophagecolony-stimulating factor, are able to enhance the cellular density ofseveral TNF superfamily ligands and/or receptors at the surface of culturedeosinophils. Finally, we have shown that native CD40L and CD30L at thesurface of purified eosinophils are functionally active and able totransduce proliferative signals on CD40+ and CD30+ target cells, includingcultured H-RS cells. Conclusions: Our data suggest that eosinophils may act as importantelements in the pathology of HD by providing cellular ligands forTNF-superfamily receptors (CD40, CD30, CD95/Fas) able to transduceproliferation and antiapoptotic signals at the surface of H-RS cells. Thepresence on eosinophils of receptors for TNF ligands expressed by activatedT cells (i.e., OX40L, FasL, CD40L, 4-1BBL), also suggest that eosinophils maycontribute to the deregulated network of interactive signals between H-RScells, T cells, and other surrounding reactive cells.
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