Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line

Abstract

The presence of a prominent tissue eosinophilia represents a typical histopathologic hallmark of Hodgkin's disease (HD). To evaluate the putative role of eosinophils on tumor cell regulation in HD, we have analyzed these cells for the functional expression of CD30 ligand (CD30L), a surface molecule able to transduce CD30-mediated proliferation signals on Hodgkin's (H) and Reed-Sternberg (RS) cells. The results demonstrate that circulating and tissue eosinophils from normal donors and patients with HD or hypereosinophilic syndrome (HES), display CD30L mRNA and express CD30L protein, as shown by immunostaining with a specific monoclonal antibody (M80) and with a biotinylated soluble CD30-Fc fusion protein. The surface density of CD30L on eosinophils from HD and HES patients was remarkably higher compared with healthy donors, probably reflecting a cytokine-mediated upregulation in these pathologic conditions. Accordingly, we provide evidence that cytokines regulating eosinophils proliferation and activation, ie, interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF), are able to enhance the cellular density of CD30L on purified eosinophils from normal subjects. Finally, we show that native CD30L on human eosinophils is a functionally active surface structure able to transduce proliferative signals on CD30+ target cells, including cultured H-RS cells. Our data suggest that eosinophils may not merely represent innocent bystanders, but rather act as important elements in the pathology of HD by contributing to the deregulated network of CD30/CD30L-mediated interactive signals between H-RS cells and surrounding reactive cells.

Retracted: Transactivation of the ICAM‐1 gene by CD30 in Hodgkin's lymphoma

“…Supershift assay of NF-jB DNA binding complex in nuclear extracts from KM-H2 cells was also carried out. Where indicated, appropriate antibodies were added to the reaction mixture (lanes [13][14][15][16].…”

“…15 In contrast, expression of its ligand CD30L is broader, being expressed on lymphocytes, neutrophils and eosinophils as well as activated monocytes/macrophages. 16,17 The functional role of CD30 under physiological conditions is not fully understood. At a clonal level, CD30 signals are pleiotropic.…”

The role of T cells in the microenvironment of Hodgkin lymphoma

“…1) [21]. Eosinophils and mast cells are CD30L positive and may contribute to NF-kB activity in HRS cells by stimulating CD30 on HRS cells [22,23]. Additional factors that stimulate HRS cells are IL-3, which is secreted by CD4 + T cells [24,25], and APRIL, that is expressed by neutrophils and binds to BCMA and transmembrane activator and calcium-modulating ligand interactor on HRS cells [26].…”

Progression of Lymphomatoid Papulosis to Systemic Lymphoma Is Associated with Escape from Growth Inhibition by Transforming Growth Factor‐β and CD30 Ligand

“…25 Recombinant CD30L expressed on the surface of cultured cells was tested for biological activities on human CD30 + lymphoma cell lines derived from Hodgkin's disease and systemic anaplastic large-cell lymphoma. 24,26 CD30L-expressing cells stimulated the proliferation of Hodgkin's disease cell lines (HDLM-2, L-540) but had a cytotoxic/antiproliferative effect on cell lines derived from systemic CD30 + ALCL (Karpas 299, TS, DHL-1). A reduction in viable cell number of ALCL cells did not appear to result from apoptosis since DNA fragmentation was not evident.…”

“…This dichotomous effect is consistent with the known pleiotropic effects of CD30 activation in other cell types. [23][24][25][26] Further experiments will test the effects of CD30 cross-linking on proliferation and apoptosis of cutaneous lymphoma cells isolated directly from regressing and nonregressing skin lesions.…”