Role of Hodgkin and Reed-Sternberg Cell-Derived Lymphotoxin-Alpha in T Cell Recruitment into the Microenvironment of Hodgkin Lymphoma Lesions

Abstract

Classical Hodgkin Lymphoma (cHL) is characterized by the presence of a minority of malignant Hodgkin and Reed-Sternberg cells (HRS cells) surrounded by massive immune infiltrates particularly, CD4+ T helper 2 cells, regulatory T cells and CD8+ cytotoxic T cells. The mechanisms underlying T cell recruitment into the lymph node lesions remain unknown. The aim of this study is to elucidate whether HRS cells can modulate endothelial cells (EC) to facilitate T cell recruitment into the cHL lesions.

Our data suggest that lymphotoxin-alpha (LTa) derived from HRS cell culture supernatant (C/S) is the dominant stimulatory factor to induce ICAM-1, VCAM-1 and E-selectin expression on ECs. Besides that, C/S stimulated ECs also enhance naive and memory T cell-endothelial cell interactions under dynamic flow conditions as well as T cell transmigration as compared to unstimulated control. LTa production by HRS cells is primarily regulated by Cox activity.