Studies on the defect in cell-mediated immunity in lepromatous leprosy using HLA-D-identical siblings. Absence of circulating suppressor cells and evidence that the defect is in the T-lymphocyte, rather than the monocyte, population.
Sixteen healthy siblings were identified as HLA-D-identical to 12 borderline lepromatous or polar lepromatous leprosy patients by the absence of a mixed lymphocyte reaction (MLR). The peripheral blood mononuclear cells (PBM) of the healthy siblings showed a lymphoproliferative response (delta cpm) to Mycobacterium leprae antigens which was about fivefold or more greater than that of the lepromatous patients. Lepromatous PBM, with or without mitomycin C treatment, were co-cultured with a constant number of normal PBM. In other experiments the two cell types were co-cultured in various proportions, with the total cell number kept constant. Neither approach revealed suppressor cells in lepromatous PBM capable of suppressing the lymphoproliferative response to M. leprae. On the contrary, we found that lepromatous PBM can respond to M. leprae antigens if the sensitized lymphocyte is provided by mitomycin-C treated normal PBM. Additionally, experiments in which isolated adherent cells and non-adherent cells of sibling pairs were recombined failed to reveal a defect in the M. leprae antigen-presenting function of lepromatous adherent cells. Since we found no evidence that sensitized cells are present in lepromatous PBM with their function unexpressed (due to a monocyte defect) or suppressed (due to suppressor cells), we conclude that lepromatous patients simply lack sufficient numbers of antigen-specific T lymphocytes to initiate a lymphoproliferative response to M. leprae antigens. The reason for their absence remains an important unanswered question.
D000293:Adolescent; D000328:Adult; D002448:Cell Adhesion; D002648:Child; D000939:Epitopes; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007918:Leprosy / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009166:Mycobacterium leprae / Q000276:immunology; D012801:Sibling Relations; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D008937:Mitomycins; D016685:Mitomycin