Abstract
Leprosy is a complex chronic, infectious dermato-neurological disease that affects the skin and peripheral nerves especially during immuno-inflammatory episodes known as type 1/T1R and type 2/T2R reactions. This study investigated the in situ expression of CD25+Foxp3+ Treg cells and TGF-β1, IFN-γ, IL-17 in leprosy T1R and T2R. Tregs were evaluated in 114 skin biopsies from 74 leprosy patients: 56 T1R (28-paired reaction-free/reactional biopsies, 28 unpaired T1R), 18 T2R (12 paired reaction-free/reactional biopsies, 6 unpaired T2R). Double CD25+Foxp3+immunostained Treg cells obtained by automated platform (Ventana BenchMark XT, Roche, Mannheim, Germany) were counted (Nikon Eclipse E400 2mm2). Cytokine expression was evaluated by immunostaining in 96 biopsies (48 paired reaction-free/reactional lesions, 24 T1R, 24 T2R) using rabbit polyclonal anti human TGF-β1, IFN-γ, IL-17 antibodies (Santa Cruz Biotechnology CA, USA). Treg cell counts in leprosy reactional lesions were higher compared to reaction-free (p = 0.002). Treg numbers were higher in T1R compared to paired unreactional T1R lesions (p = 0.001). Similar frequency of Treg was seen in paired reactional versus unreactional T2R lesions. Higher expression of TGF-β, IFN-γ and IL-17 was seen in T2R lesions compared to T1R and reaction-free lesions. The increase in Treg cells during T1R suggests a suppressive role to control the exacerbated cellular immune response during T1R that can cause tissue and nerve damage. Evidences of upregulated Treg cells in TR1, which usually occurs in patients with Th1-Th17 immunity and the indications of the expression of Th17/IL-17 in T2R, which develops in patients with Th2-Treg profile, suggest plasticity of Treg-Th17 cells populations and a potential role for these cell populations in the immunopathogenesis of leprosy reactions.
Highlights
Leprosy is a complex chronic, infectious dermato-neurological disease that affects the skin and peripheral nerves
CD25+Foxp3+T regulatory cells (Treg) cell numbers in T1R, T2R compared to reaction-free lesions
Our study evaluated the in situ expression of both double positive CD25+ Foxp3+ Treg cells and cytokines in leprosy T1R and T2R with special emphasis on the frequency of Treg cells in paired biopsies collected in the absence of reaction and during the course of a reactional episode
Summary
Leprosy is a complex chronic, infectious dermato-neurological disease that affects the skin and peripheral nerves. The disease is characterized by a wide spectrum of clinical, immunologic, microbiologic and histopathologic manifestations which can be classified as tuberculoid (TT), borderline tuberculoid (BT), borderline-borderline (BB), borderline lepromatous (BL) and lepromatous leprosy [4]. Paucibacillary patients (PB) that comprise TT and BT forms, present low bacillary load, few localized lesions and develop inflammatory Th1 type and Th17 cell-mediated immunity (CMI) to M. leprae with low antibody production [6,7,8]. On the other end of the spectrum, multibacillary patients (MB), which include BB, BL and LL forms, show multiple skin lesions, high bacillary load, Th2 type immunity with vigorous antibody production and higher expression of Treg cells [9,10,11,12]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.