Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells

Autor(es)

Vieira, Ana Paula ^[1] ; Bianconcini Trindade, Maria Angela ^{[2, 3]} ; Pagliari, Carla ^[4] ; Avancini, Joao ^[3] ; Sakai-Valente, Neusa Yurico ^[3] ; da Silva Duarte, Alberto Jose ^{[1, 4]} ; Benard, Gil ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Div Clin Dermatol, Lab Med Invest Unit 56, BR-05403 Sao Paulo, SP - Brazil

^[2] Sao Paulo State Hlth Dept, Hlth Inst, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Div Clin Dermatol, BR-05403 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sch Med, Dept Pathol, BR-05403 Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Trop Med, Lab Med Invest Unit 53, BR-05403 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: American Journal of Tropical Medicine and Hygiene; v. 94, n. 4, p. 721-727, APR 2016.
• Citações Web of Science: 14

Resumo

Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-beta-expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL -17 expression but decreased TGF-beta expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3 + (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper -17 responses that characterize this reaction. (AU)

• Processo FAPESP: 14/15286-0 - Atuação de células T reguladoras em episódios reacionais na hanseníase
• Beneficiário: Gil Benard
• Linha de fomento: Auxílio à Pesquisa - Regular