Involvement of regulatory T cells in the immunosuppression characteristic of patients with paracoccidioidomycosis

• Grant number: 10/12415-2
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: October 01, 2010
• End date: March 31, 2011
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ronei Luciano Mamoni
• Grantee: Ronei Luciano Mamoni
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Patients with paracoccidioidomycosis (PCM) exhibit suppression of cellular immune response characterized by negative DTH to Paracoccidioides brasiliensis antigens, apoptosis of lymphocytes and high expression of CTLA-4, IL-10 and 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) and patients who had received treatment (TD). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C) and also had elevated expression of regulatory markers (GITR, CTLA-4, CD95L, LAP-1 and CD38). Analysis of regulatory activity showed that Treg cells from the AD group had greater activity than cells from the other groups and that cell-cell contact is mandatory for this activity in group C, but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL10 and anti-TGF-beta neutralizing antibodies to the cultures showed that production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated number of these cells with increased regulatory phenotype and strong suppressive activity suggests 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)