Modulation of Costimulatory Molecules on Follicular Lymphoma Cells by TNF and CD40

Abstract

TNF has recently been implicated in the formation of germinal center cells in lymphoid organs. Follicular lymphoma (FL) is thought to represent the pathological counterpart of germinal center B-cell. High levels of TNF and its soluble receptors were found in the plasma of FL patients whereas the transcripts of these molecules were previously found to be present in FL patients lymph nodes. We therefore studied here the effects of TNF on the expression of costimulatory molecules implicated in the cytotoxic T cell response on purified FL cells. In contrast to results described with B-type chronic lymphocytic leukemia, also characterized by high levels of circulating TNF, none of the tested samples showed a regulation of CD80, CD86, CD27 and CD70 in response to TNF. To confirm that the lack of regulation of these molecules was not due to the FL cells inability to modulate their expression, we therefore analyzed costimulatory molecules expression after CD40 pathway stimulation. After culture with human CD40L-transfected L-cells, an up-regulation of CD80, CD86 and CD70 expression was observed, while TNF addition in this model did not influence these changes. In this context, the CD27 molecule was down-regulated except in a single case, where its expression was increased.

Taken together, this data demonstrates that in vitro expression of costimulatory molecules such as CD80, CD86, CD27 and CD70, which are implicated in the anti-tumoral response, can be regulated by CD40 ligand but not by TNF.

Key Words:

• Lymphoma
• anti-tumor immunity
• tumor necrosis factor
• CD80
• CD86
• CD27
• CD40
• co-stimulatory molecules