SURFACE PHENOTYPE OF LANGERHANS CELLS AND LYMPHOCYTES IN GRANULOMATOUS LESIONS FROM PATIENTS WITH PULMONARY HISTIOCYTOSIS-X

Pulmonary histiocytosis X (HX) is a disorder characterized by the pres ence of granulomas in which Langerhans cells (LC) and lymphocytes are abundant. Although the pathogenesis of pulmonary HX remains unknown, a n uncontrolled immune response initiated by LC, which are potent antig en-presenting cells in vitro, may play an important role. To further c haracterize LC and lymphocytes present in granulomas from these patien ts, we used immunohistochemical techniques and monoclonal antibodies t o evaluate the surface phenotype and electron microscopy (EM) to seek evidence for close interactions between both cell types in these lesio ns. In all samples, HX granulomas contained large numbers of strongly positive CD1a cells in which typical Birbeck granules were identified by EM. The number of Birbeck granules in LC from HX granulomas was str ikingly increased compared with that in LC in the bronchioles of norma l subjects. Furthermore, unlike normal LC, essentially all LC in HX gr anulomas expressed CD4 antigens and were strongly positive for CD1c. L ymphocytes infiltrating HX granulomas were almost entirely CD3+ T cell s and were mainly CD4 positive (CD4/CD8 ratio 3.7 +/- 1.3). These T ly mphocytes expressed almost exclusively alpha/beta T cell receptors, an d gamma/delta T cells were rarely observed (< 5% of CD3+ cells). In ar eas of lymphocytic infiltration, close differentiated contacts between LC and lymphocytes were observed by EM in all samples. These results demonstrate that interactions between activated LC and CD4+ T lymphocy tes are prominent in early HX granulomas and support the idea that an immune response in which LC serve as accessory cells is involved in th e pathogenesis of this disorder