ABSTRACT
AIMS: To evaluate the role of Langerhans cells (LCs) in the local activation of leprosy lesions. LCs, acting as tolerance inducers and immune stimuli, are dendritic cells recently implicated in cutaneous homeostasis. The role of LCs in the defence against mycobacterial infection remains poorly understood. METHODS AND RESULTS: The number and distribution of CD1a+ skin cells and HLA-DR and intercellular adhesion molecule (ICAM)-1 expression were analysed in leprosy skin lesions and in delayed-type hypersensitivity (DTH) tests. The results showed a high number of LCs in tuberculin and lepromin tests, in tuberculoid lesions and in the epidermis and dermis during type I and II reactions. In multibacillary lesions, however, the number of LCs was consistently low in comparison with other groups. Increased numbers of LCs were accompanied by marked HLA-DR and ICAM-1 expression, suggesting a strong relationship between these immunological events. CONCLUSIONS: CD1a+ cells are implicated in the local immunological events taking place after mycobacterial stimuli and may account for the local activation of all types of reactional episodes in leprosy.
Subject(s)
Langerhans Cells/immunology , Leprosy, Lepromatous/immunology , Antigens, CD1/metabolism , HLA-DR Antigens/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Langerhans Cells/pathology , Leprosy, Lepromatous/pathology , Mycobacterium leprae/immunology , Mycobacterium leprae/pathogenicity , Skin/immunology , Skin/pathologySubject(s)
Male , Humans , Cytokines/biosynthesis , Cytokines/genetics , RNA-Directed DNA Polymerase , Erythema Nodosum/immunology , Erythema Nodosum/pathology , Gene Expression , Tumor Necrosis Factor-alpha/metabolism , Leprosy, Lepromatous/immunology , Leprosy, Lepromatous/pathology , RNA, Messenger/genetics , Polymerase Chain ReactionABSTRACT
Studies were caried out to determine the effect of intra-dermal injections of recombinant human interferon-gamma (rIFNy) on the viability of Mycobacterium leprae. Twenty-three untreated and 4 treated multibacillary patients, 12 with lepromatous leprosy (LL) and 15 with bordeline lepromatous leprosy (BL), were selected for intradermal administration of rIFNy or PPD. Treated patients (LL and BL) had received multi-drug therapy according to the recommendations of the World Health Organization, i. e., rifampicxin (600 mg/month), dapsone (100 mg/day) and clofazimine (50 mg/day and 300 mg/month) for 1-4 months. Three daily doses of 10 or 30 ug rIFNy induced local induration and mononuclear leucocyte accumulation. Bacteria isolated from a punch biopsy of the site 21 days after lymphokine administration were injected into mouse foot pads and evaluated for viability and growth. The local response to rIFN (specific activity 2 x 10 7 units/mg protein) induced a delay or total inhibition of M. leprae growth in the mouse foot pad, ,indicating that the cellular response to the antigen reduced local M. leprae viability. The extent of reduction in viability depended on the dose of rIFNy injected and the extent of local induration induced by the lymphokine. With a vigorous cell-mediated immune response growth was fully inhibited. A similar but less extensive effect on M. leprae viability was observed in resapo0nse to the local injection of 5 units in 0.1 ml of purified protein derivative of tuberculin (PPD)
