Regulatory T Cells in Leprosy: Implications for Immune Response and Pathogenesis

Abstract

This study investigates the role of regulatory T cells (Tregs) in the inability to control pathogen propagation in severe chronic granulomatous diseases, focusing on leprosy. Study examined 28 newly diagnosed leprosy patients, including 16 with lepromatous leprosy and 12 with tuberculoid leprosy, along with six healthy individuals exposed to Mycobacterium leprae. Immunohistochemistry and flow cytometry were used to identify Tregs in peripheral blood mononuclear cells (PBMCs) stimulated with M. leprae antigenic preparation and phytohemagglutinin in vitro, as well as in skin lesions. Stimulated PBMCs expressed IL-10, TGF-β, and CTLA-4 and displayed lymphoproliferative, interleukin-10, and interferon-gamma responses in vitro. Study findings show that M. leprae antigens significantly reduced lymphoproliferative responses (LPR) in lepromatous patients and their contacts but significantly increased the likelihood of T cell development. No significant differences were observed in mitogen-induced Tregs and LPRs among the three patient groups. Higher levels of TGF-β and IL-10, correlating with a higher number of Tregs, were observed in lepromatous patients. In lepromatous lesions, histiocytes were vacuolized throughout, while Tregs were generally absent in tuberculoid lesions. The presence of numerous Tregs in patients with uncontrolled bacillary multiplication suggests a critical role of Tregs in the progression of lepromatous leprosy, contrasting with their absence in patients who limit M. leprae growth. This study highlights the importance of Tregs in the pathogenesis of leprosy and their potential impact on disease management.