Involvement of Regulatory T Cells in the Immunosuppression Characteristic of Patients with Paracoccidioidomycosis

Autor(es)

Ferreira, Maria Carolina ^[1] ; Dias de Oliveira, Romulo Tadeu ^[1] ; da Silva, Rosiane Maria ^[1] ; Souza Lima Blotta, Maria Heloisa ^[1] ; Mamoni, Ronei Luciano ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Dept Clin Pathol, Fac Med Sci, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Infection and Immunity; v. 78, n. 10, p. 4392-4401, OCT 2010.
• Citações Web of Science: 29

Resumo

Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to Paracoccidioides brasiliensis antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor beta (TGF-beta). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoid-induced tumor necrosis factor {[}TNF] receptor-related protein {[}GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-beta neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role. (AU)

• Processo FAPESP: 07/50183-3 - Avaliação da participação de células T regulatórias naturais (CD4+ CD25+) na imunossupressão observada em pacientes com paracoccidioidomicose
• Beneficiário: Maria Heloisa Souza Lima Blotta
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/59624-0 - Avaliação da participação das células T regulatórias naturais (CD4+CD25+) na imunossupressão observada em pacientes com paracoccidioidomicose
• Beneficiário: Maria Carolina Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado