Reed-Sternberg cell-derived lymphotoxin-α activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma.

[hodgkin lymphoma, classical]

It is known that cells within the inflammatory background in classical Hodgkin lymphoma (cHL ) provide signals essential for the continual survival of the neoplastic Hodgkin and Reed -Sternberg (HRS ) cells . However , the mechanisms underlying the recruitment of this inflammatory infiltrate into the involved lymph nodes are less well understood . In this study , we show in vitro that HRS cells secrete lymphotoxin-α (LT α ) which acts on endothelial cells to upregulate the expression of adhesion molecules that are important for T cell recruitment . LT α also enhances the expression of hyaluronan which preferentially contributes to the recruitment of CD 4 (+) CD 4 5 RA (+) naïve T cells under in vitro defined flow conditions . Enhanced expression of LT α in HRS cells and tissue stroma ; and hyaluronan on endothelial cells are readily detected in involved lymph nodes from cHL patients . Our study also shows that although NF-κB and AP -1 are involved , the cyclooxygenase (COX ) pathway is the dominant regulator of LT α production in HRS cells . Using pharmacological inhibitors , our data suggest that activity of COX 1 , but not of COX 2 , directly regulates the expression of nuclear c-Fos in HRS cells . Our findings suggest that HRS cell-derived LT α is an important mediator that contributes to T cell recruitment into lesional lymph nodes in cHL .