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DOWNMODULATION OF REGULATORY T CELLS PRODUCING TGF-B PARTICIPATES IN PATHOGENESIS OF LEPROSY REACTIONS
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Patologia e Laboratórios. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Patologia e Laboratórios. Rio de Janeiro, RJ, Brasil.
Abstract
Leprosy reactions are an acute and systemic manifestation, which occurs suddenly,
can be severe and lead leprosy patients to disability. Reactional episodes are observed
among half of the multibacillary patients, mainly in borderline lepromatous and
lepromatous forms. They may begin at any time during multidrug therapy, and even
before the treatment. Physical disabilities, which are the source of extreme suffering
and pain for patients, occur in progression of the cellular immune response associated
with a reaction and are still poorly understood. Thus, this work aimed to phenotypically
and functionally characterize CD4+ and CD8+ Treg cells ex vivo and in response to
Mycobacterium leprae (ML). We studied 52 individuals, including 18 newly diagnosed
and untreated multibacillary leprosy patients, 19 reactional multibacillary patients (Type
I or Type II episodes) and 15 healthy volunteers, included as controls, all residents
of the city of Rio de Janeiro. The functional activity and frequencies of these cells
were evaluated through multiparametric flow cytometry. In addition, the production of
cytokines in supernatant from peripheral blood mononuclear cell cultures was also
investigated against ML by enzyme-linked immunosorbent assay. Our results showed a
decrease in CD4+TGF-b+ Treg and CD8+ TGF-b+ Treg in leprosy multibacillary patients
during both types of reactional episodes. Alterations in the cytokine profile was also
observed in Type II reactions, along with upregulation of IL-17 and IL-6 in supernatant.
Thus, our study suggests that downregulation of Treg cells is related with both classes
of reactional episodes, improving our understanding of immune hyporesponsiveness in
multibacillary patients and hyperesponsiveness in both reactions.
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