McLelland, Janet; (1990) Studies relating to Langerhans cell histiocytosis. Doctoral thesis (M.D.), University College London.

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Abstract

Langerhans cell histoscytosis (LCH) is an uncommon disease of unknown aetiology, where characteristic histiocyte cells, designated LCH cells, accumulate in various tissues. This thesis examines the clinical, diagnostic and immunological features of LCH. In a clinical study of 60 children with LCH, a new disease scoring system was compared with the existing Lahey system and found to be better at predicting outcome. The efficacy of the current treatment protocol used in the UK was compared with that of other International Centres where more aggressive therapeutic approaches are used. Diagnostically, two markers for LCH cells were compared in paraffin-embedded tissue. Peanut agglutinin was found to be more specific and as easy to use as the S100 stain. Mouse monoclonal antibodies were produced against LCH cells but none proved specific. Immunological studies defined the functional characteristics of normal Langerhans cells and compared these with the functional characteristics of LCH cells. Epidermal cells containing 1% Langerhans cells were shown to be as potent as enriched blood dendritic cells at presenting recall antigen to autologous T-cells, and 16 times more potent than monocytes in this system. LCH cells, however, failed to act as accessory cells in mitogen driven T cell stimulation. In order to provide a source of cells to examine LCH function an attempt was made to produce an LCH cell line. Fresh LCH cell from 10 patients with LCH were cultured under different conditions and with a variety of growth factors. Only one cell line was generated, which was shown by enzyme histochemistry to be histiocytic, but this was immature and attempts to induce maturation failed. The nature of LCH (malignant or reactive) is controversial. Flow cytometry of fresh and paraffin-embedded LCH cells demonstrated that LCH cells are diploid supporting a reactive nature of this disease.

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