Role of regulatory T-cells in Hansen’s disease: A systematic review

Leprosy represents a significant challenge in understanding the multiple immunological mechanisms that influence the distinct clinical forms. This integrative review used the electronic databases MEDLINE/PubMed and the Virtual Health Library (VHL), including 12 studies conducted predominantly in Brazil, China, India, and Ethiopia. We focused on the role of regulatory T (Treg) cells in Hansen's disease, specifically examining their frequency of expression and the functional characteristics of their subpopulations. Findings reveal the ubiquitous nature of Treg across clinical forms, particularly the CD3+CD4+CD25+FoxP3+ phenotype, with a pronounced frequency in multibacillary cases, including borderline-lepromatous and lepromatous leprosy. In these cases, a notable upregulation of inhibitory molecules (CTLA-4, PD-1) and the production of immunoregulatory cytokines (IL-10, TGF-β) are evident in skin lesions and/or in vitro-cultured cells. The intricate interplay of local stimuli, cytokine profiles, antigenic nature, receptor expressions, co-inhibitory molecules, and macrophage types modulates the cellular immune response, influencing disease severity. The increased presence of Treg and their associated products appears to contribute to bacillary multiplication in patients with the disseminated form, fostering disease persistence. This comprehensive review enhances our understanding of Hansen's disease pathogenesis, shedding light on potential avenues for targeted therapeutic interventions.