Hodgkin and Reed-Sternberg cells modulate endothelial cell function in classical Hodgkin lymphoma

Abstract Growth and survival of neoplastic Hodgkin and Reed-Sternberg cells (H-RS) cells in classical Hodgkin lymphoma (cHL) is dependent on cell-cell contact and soluble mediator signals derived from the inflammatory infiltrate within the lesion. However, the mechanisms underlying recruitment of the inflammatory infiltrate, particularly T cells, into lesional lymph nodes remain unclarified. In this study, we test the hypothesis that H-RS cells secrete soluble mediators to induce endothelial cell (EC) activation to modulate T cell recruitment in cHL. We examined in-vitro interactions, under static and flow conditions, between freshly isolated T cell subsets and EC treated with conditioned medium (CM) harvested from the H-RS cell line, KM-H2. Both CM-stimulated EC and TNFα-stimulated EC support CD4+ naive and memory T-cell interactions under flow conditions. Both CD4+ naive and memory T cell demonstrated enhanced transmigration across CM-stimulated EC monolayers in response to CXCL12 as compared to TNFα-stimulated or unstimulated EC. Our data show that the upregulation of inducible adhesion molecules on CM-stimulated EC is dependent on the NFκB pathway; but the dominant mediator involved is not TNFα. However, blockade of cyclooxygenase activity in KM-H2 cells partially attenuated the efficacy of the CM in activating EC. These findings suggest that H-RS cells secrete soluble mediators that can modulate endothelial cell function and influence recruitment of T cells into the cHL lesion.