Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions

The pathogenesis of Langerhans cell histiocytosis (LCH) is obscure, partly because the events leading to activation of Langerhans-like lesional cells (LCH cells) and associated T cells, and the excessive cytokine production b y these cells are unknown. The interaction between CD40 on antigen-presenti ng cells (APC) like Langerhans cells and CD40 ligand (CD40L) (CD154) expres sed by activated CD4+ T cells, is essential for the activation of both the APC and the T cells and results in upregulation of APC functions and initia tion of immunoreactivity. The effects of CD40-CD40L interaction include inc reased expression of co-stimulatory and adhesion molecules, proliferation, and production of pro-inflammatory cytokines and proteolytic enzymes, all f eatures of LCH. Using immunohistochemistry, we analysed the irt situ presen ce of the co-stimulatory molecules CD40 and CD40L in 15 fresh frozen biopsi es of LCH lesions in children. The cells producing these molecules were ide ntified by double staining for CD1a on LCH cells and CD3 on T cells. Promin ent expression of CD40 by LCH cells and CD40L by T cells was found in all 1 5 specimens regardless of the source of specimen or characteristics of the patient. The findings of high expression of CD40 and CD40L in all specimens imply a key role for the CD40-CD40L adhesion pathway in the pathogenesis o f LCH. Since this interaction is an accessible and realistic target for imm unotherapy, these findings prompt speculation on the use of blocking antibo dies to CD40 or to CD40L in the treatment of LCH. (C) 2000 Elsevier Science Ltd. All rights reserved.