T regulatory cells in leprosy reactional episodes

• Grant number: 14/15286-0
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2015 - February 28, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Gil Benard
• Grantee: Gil Benard
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Maria Angela Bianconcini Trindade

Abstract

Leprosy, caused by the bacillus Mycobacterium leprae, is a chronic transmissible disease with lesions of the skin, peripheral nerves and mucosa. The outcome of the infection and its clinical manifestations are driven by several factors, including the host immune response to the pathogen. The infection can progress to either the resistant pole (tuberculoid), to the susceptible pole (lepromatous pole), or to instable forms of the disease (borderline forms) which not infrequently is associated with reaction episodes. These episodes correspond to acute inflammatory exacerbations that may result in permanent neural damage and irreversible physical handicaps. Treatment of this condition is difficult and based on immunosuppressive drugs with many severe adverse effects (corticosteroids and talidomide). The hypothesis is that there is a loss of regulation of the immune response of the patients who develop reaction episodes, which would be due to deficiency in the number and/or function of T regulatory cells (Treg). These cells display potent mechanisms that are crucial for the regulation of the immune responses and its suppressor function is mediated either through molecules such as CTLA-4 and CD39 or through cytokines such as IL-10 and TGF- ². However, it is not clear up to know the role played by these cells in the reaction episodes. The aim of the project is to determine by immunohistochemistry the frequency of Treg in situ (biopsies of lesions from patients with reaction), evaluate the frequency and function of Treg in the peripheral blood of these patients, as well as the potential for in vitro induction/expansion of these cells. A better understanding of the role of Treg in reaction episodes can potentially contribute to the improvement of their treatment by introducing novel immunotherapies. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES, JULIANA RUIZ; BERTO MARQUES DA SILVA, CIBELE CRISTINE; DA SILVA, ALINE GRANDI; DE CARVALHO PINTO, REGINA MARIA; DA SILVA DUARTE, ALBERTO JOSE; CARVALHO, CELSO RICARDO; BENARD, GIL. Effect of an Exercise Program on Lymphocyte Proliferative Responses of COPD Patients. Lung, v. 196, n. 3, p. 271-276, JUN 2018. (14/15286-0)

VIEIRA, ANA PAULA; BIANCONCINI TRINDADE, MARIA ANGELA; PAGLIARI, CARLA; AVANCINI, JOAO; SAKAI-VALENTE, NEUSA YURICO; DA SILVA DUARTE, ALBERTO JOSE; BENARD, GIL. Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells. American Journal of Tropical Medicine and Hygiene, v. 94, n. 4, p. 721-727, APR 2016. (14/15286-0)

VIEIRA, ANA PAULA; BIANCONCINI TRINDADE, MARIA ANGELA; DE PAULA, FLAVIO JOTA; SAKAI-VALENTE, NEUSA YURICO; DA SILVA DUARTE, ALBERTO JOSE; CARVALHINHO LEMOS, FRANCINE BRAMBATE; BENARD, GIL. Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?. BMC INFECTIOUS DISEASES, v. 17, APR 24 2017. (14/15286-0, 16/08730-6)

CARDONA, CAROL; VIEIRA, ANA P.; AVANCINI, JOAO; DUARTE, ALBERTO J. S.; TRINDADE, MARIA ANGELA B.; BENARD, GIL. Expansion and suppressive capacity of regulatory T cells isolated from patients across the leprosy spectrum: a pilot study. Microbes and Infection, v. 22, n. 8, p. 349-355, SEP 2020. (14/15286-0)

MIYASHIRO, DENIS; VIEIRA, ANA PAULA; BIANCONCINI TRINDADE, MARIA ANGELA; AVANCINI, JOAO; SANCHES, JOSE ANTONIO; BENARD, GIL. A case report of erythroderma in a patient with borderline leprosy on reversal reaction: a result of the exacerbated reaction?. BMC DERMATOLOGY, v. 17, DEC 20 2017. (14/15286-0)