Delineation of a human T cell subset responsible for lepromin-induced suppression in leprosy patients.

Abstract

Abstract The selective immunologic unresponsiveness in patients with lepromatous leprosy to antigens of Mycobacterium leprae offers a unique opportunity for probing the mechanisms of regulation of specific immune responses in man. We have previously reported that Dhar-mendra lepromin induces in vitro suppression of the mitogenic response of mononuclear cells to Con A from lepromatous and borderline but not tuberculoid leprosy patients or normal donors. M. leprae-induced suppression in vitro was produced by an adherent cell and an E-rosetting cell. In the present studies, T cells from lepromatous patients were separated into TH2+ and TH2− subsets identified by absorbed anti-thymocyte globulin using the fluorescence-activated cell sorter (FACS). The whole T cell population and the separated TH2+ and TH2− subsets were tested for M. leprae-induced suppressor activity by admixing with mononuclear cells from normal donors and challenging in vitro with antigen and mitogen. Again, Dharmendra lepromin had no effect on the mitogenic responses of normal mononuclear cells to Con A. However, in lepromatous and borderline leprosy patients, the TH2+ subset, constituting approximately 20% of the total T cells, exerted lepromin-induced marked suppression of normal donors’ lymphocytes, and all the suppressor activity in the patients’ cells appeared exclusively in the TH2+ subset. Of interest was the finding that no significant suppression was produced by the TH2+ subset treated under comparable conditions obtained from tuberculoid leprosy patients or normal individuals. The identification of a suppressor subpopula-tion of T cells in lepromatous patients by specific anti-sera raises the possibility of a novel therapeutic approach to this and related diseases.