In Situ T Regulatory Cells And Th17 Cytokines In Paired Samples Of Leprosy Type 1 And Type 2 Reactions

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(+)T(reg) cells and TGF-beta 1, IFN-gamma, IL-17 in leprosy T1R and T2R. T-regs 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 T-reg cells obtained by automated platform (Ventana BenchMark XT, Roche, Mannheim, Germany) were counted (Nikon Eclipse E400 2mm(2)). 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-beta 1, IFN-gamma, IL-17 antibodies (Santa Cruz Biotechnology CA, USA). T-reg cell counts in leprosy reactional lesions were higher compared to reaction-free (p = 0.002). T-reg numbers were higher in T1R compared to paired unreactional T1R lesions (p = 0.001). Similar frequency of T-reg was seen in paired reactional versus unreactional T2R lesions. Higher expression of TGF-beta, IFN-gamma and IL-17 was seen in T2R lesions compared to T1R and reaction- free lesions. The increase in T-reg 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 T-reg 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-T-reg profile, suggest plasticity of T-reg-Th17 cells populations and a potential role for these cell populations in the immunopathogenesis of leprosy reactions.