FUNCTIONAL DEFECT IN CELLS INVOLVED IN LANGERHANS CELL HISTIOCYTOSIS

The characteristic cell type involved in Langerhans cell histiocytosis , 'LCH cells', express most of the enzyme histochemical and immunocyto chemical markers of normal epidermal Langerhans cells. It is not known , however, whether these LCH cells express the functional characterist ics of normal epidermal Langerhans cells. We studied the alloantigen-p resenting activity of LCH cells derived from lesional sites of three p atients with the disease. Lesional cells expressing the CD1a molecule were enriched using either fluorescein-activated cell sorting or negat ive selection with indirect immunomagnetic beads, and functional activ ity was assessed using the 6-day primary allogeneic mixed-cell reactio n. Compared to epidermal Langerhans cells from healthy controls, LCH c ells showed minimal alloantigen-presenting activity on a per-cell basi s. The diminished activity was not reversed by exogenous prostaglandin synthetase inhibitor or recombinant human IL-1 beta. This study confi rms our previous report of a child, with fatal multisystem Langerhans cell histiocytosis suggesting that this disease represents a condition in which functionally defective cells of Langerhans cell phenotype ac cumulate and/or proliferate in various tissues. We postulate that the functional defect is a primary defect of these LCH cells that have acq uired an as-yet-undetermined biological insult(s).