Learning from Lesions: Patterns of Tissue Inflammation in Leprosy

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-02, Vol.85 (4), p.1213-1217
• Main Authors: Modlin, Robert L., Melancon-Kaplan, Johanne, Summer M. M. Young, Pirmez, Claude, Kino, Hironori, Convit, Jacinto, Rea, Thomas H., Bloom, Barry R.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; Antigens; Antigens, Differentiation, T-Lymphocyte - analysis; Bacterial diseases; Biological and medical sciences; Blood; Cells, Cultured; Granuloma; Granuloma - pathology; Human bacterial diseases; Humans; Immunity, Cellular; Immunology; Infectious diseases; Inflammation; Interleukin-2 - pharmacology; Leprosy; Leprosy - immunology; Leprosy - pathology; Lesions; Lymphocyte Activation; Lymphocytes; Medical sciences; Monoclonal antibodies; Mycobacterium leprae; Phenotype; T lymphocytes; T-Lymphocytes - classification; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tropical bacterial diseases; Tropical medicine; Tuberculoid leprosy
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.4.1213

The clinical forms of leprosy constitute a spectrum that correlates closely with the degree of cell-mediated immunity. Patients with tuberculoid leprosy develop strong cell-mediated responses and have only a few, localized lesions, whereas patients with multibacillary lepromatous leprosy are specifically unresponsive to antigens of Myobacterium leprae. T cells of the CD4+ subset predominate in tuberculoid lesions, whereas CD8+ cells predominate in lepromatous lesions. Monoclonal antibodies that distinguish subpopulations of CD4+ and CD8+ cells were used to analyze the distribution of T cells infiltrating lesions across the disease spectrum. In lepromatous lesions, T cells of T-suppressor phenotype (9.3-) were the predominant CD8+ cells and suppressor/inducer cells (2H4+, Leu-8+) represented half of the CD4+ subset. In tuberculoid lesions, helper T cells (CD4+ 4B4+) outnumbered suppressor/inducer T cells by 14:1, compared with a ratio of 1.2:1 in peripheral blood. Analysis of the precursor frequency of antigen-reactive T cells permitted us to estimate that there was a 100-fold enrichment of T cells able to proliferate in response to M. leprae antigens in tuberculoid lesions (2/100), when compared with blood from the same patients. The methods used here to characterize the T-lymphocyte subsets and frequency of antigen-reactive T cells in leprosy may be useful in analyzing imunological reactions occurring in lesions of other inflammatory and autoimmune diseases.