Activated suppressor T cells in leprosy

Leprosy is a special disease in which the patients at the lepromatous end display selective immunologic unresponsiveness to antigens of M. leprae. We have previously explored the possibility that the anergy in lepromatous leprosy is mediated by suppressor cells. An in vitro system was developed in which lepromin induces suppression of the mitogenic response of lepromatous and borderline but not tuberculoid leprosy patients to concanavalin A. Two populations, an adherent cell and a T lymphocyte, were responsible for this lepromin-induced in vitro suppression. All the T cell suppressor activity was associated with a 20 to 30% subset of human T cells recognized by a TH₂ xenogeneic antithymocyte serum or OKT8 monoclonal antibodies. That the lepromin-induced TH₂⁺/OKT8^- subset may be involved in suppressing the specific antigenic response of peripheral blood lymphocytes of some lepromatous and borderline leprosy patients to M. leprae antigens was established by showing that OKT8-depleted cells from six of twenty-one lepromatous patients showed markedly enhanced ³H-thymidine incorporation at 6 days upon stimulation with lepromin, compared to the unresponsiveness of their unfractioniated cells. The expression of Ia determinants and Fc receptors on T cell subsets was examined as a potential marker for in situ activation. In contrast to normal subjects, there were significantly elevated numbers of Ia⁺ TH₂⁺/OKT8⁺ T cells in lepromatous leprosy patients. There was a similar elevation in FcR⁺ cells in the same subset, and the expression of Ia and of FcR were highly correlated. The possibility that the Ia and Fc markers may serve as an index of active T cell suppressor activity in vivo was strengthened by studies in a small number of lepromatous patients vaccinated with living BCG and killed M. leprae who showed marked clinical improvement and conversion to skin test positive reactivity. In ten such patients examined over a treatment period of 1 to 2 yr, the suppressor activity returned to normal levels, and the number of Ia⁺, T cells in seven of eight similarly returned to normal levels.