CD40 LIGAND EXPRESSION IN MYCOSIS-FUNGOIDES IS RESTRICTED TO THE PATCH PLAQUE (EPIDERMOTROPIC) STAGES/

CD40 ligand (CD40L) is a member of the tumor necrosis factor ligand su perfamily, It may play an intricate role in the immune response by fun ctional interaction with CD40 antigen expressed on the surface of B-ce lls, T-cells, monocytes, macrophages, antigen-presenting cells, endoth elial cells and some epithelial cells, A possible role of CD40L in the pathogenesis of non-Hodgkin's lymphoma (NHL) has been recently hypoth esized; in fact, CD40L antigen can be constitutively expressed by the neoplastic CD4(+) T-cell of nodal NHL, thus possibly having a physiolo gical role in these neoplasms, We studied the immunophenotypic and gen otypic expression of CD40L antigen in different phases of mycosis fung oides - the prototype of cutaneous T-cell lymphoma - in order to inves tigate the possible significance and role of this molecule in its path omechanism. On frozen sections, CD40L(+) T-cells were present in 9/10 specimens from patch/plaque stage mycosis fungoides. Their percentage (10-25%) and location (junctional and basal epidermal) were very simil ar to those of CD25(+) and Ki67(+) (proliferating) cells. In 5/5 speci mens from tumor stage mycosis fungoides, no CD40L immunostaining was f ound. All patch/plaque stage mycosis fungoides (6/6 specimens) contain ed the mRNA transcript for CD40L, It was never detected in tumor stage mycosis fungoides (4/4 specimens), These findings suggest that in ear ly mycosis fungoides, CD40L(+) T-cells home into the skin by interacti on with CD40(+) endothelial cells and into the epidermis by interactio n with CD40(+) basal epidermal cells. The interaction between CD40L(+) T-cells and CD40(+) Langerhans cells and the CD40/CD40L autocrine sti mulus possibly triggers activation, growth and neoplastic enhancement of T-cells, up to the blastic transformation occurring at the tumor st age, when neoplastic T-cells loose their antigenic and functional feat ures of mature T-cells and proliferate without any significant control .