Increased Frequency of CD4 and CD8 Regulatory T Cells in Individuals under 15 Years with Multibacillary Leprosy

Background: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceara state, Brazil, reflects the difficulty of its control. the spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4(+)/CD8(+)CD25(high)FOXP3(+) and CD4(+)/CD8(+)CD25(high)FOXP3(high) cells in leprosy patients and household contacts, in both cases under 15 years old.Methodology/Principal Findings: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4(+)/CD8(+) Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4(+)FOXP3(+) (21.93 +/- 8.43 vs. 13.79 +/- 8.19%, p = 0.0500), CD4(+)FOXP3(high) (10.33 +/- 5.69 vs. 5.57 +/- 4.03%, p = 0.0362), CD8(+)FOXP3(+) (13.88 +/- 9.19 vs. 6.18 +/- 5.56%, p = 0.0230) and CD8(+)FOXP3(high) (5.36 +/- 4.17 vs. 2.23 +/- 2.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients.Conclusions/Significance: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4(+) and CD8(+) Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection.Fundacao Cearense de Apoio ao Desenvolvimento Cientifico e TecnologicoPost-Graduation Program in Medical MicrobiologyUniv Fed Ceara, Dept Pathol & Legal Med, Med Lab Immunol, Fortaleza, Ceara, BrazilDermatol Ctr Dona Libania, Fortaleza, Ceara, BrazilWalter Cantidio Univ Hosp, Fortaleza, Ceara, BrazilUniv Fortaleza, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc