Regulatory T cell, CD4 + CD25 + and NKT cells in severe sepsis and septic shock

• Grant number: 08/57846-0
• Support type: Scholarships in Brazil - Master
• Effective date (Start): July 01, 2008
• Effective date (End): July 31, 2008
• Field of knowledge: Biological Sciences - Immunology
• Principal researcher: Niels Olsen Saraiva Câmara
• Grantee: Érica Fernandes de Sousa
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Sepsis is a systemic inflammatory response to infection. Recently, besides well established support strategies for the treatment of sepsis, it is still considered a major cause of death in the non-coronary Intensive Care Units. In sepsis, the inflammatory Thl cytokines (TNF-α, INF-γ, IL-2) and anti-inflammatory Th2 ones (IL-4, IL-10) can act simultaneously in a fine balance. However, recently data demonstrated that this profile of response can be modulated by the presence of specific cell populations such as regulatory CD4+CD25+ T and the NKT cells. Regulatory T cells (Tregs) can suppress through the induction of IL-10 or TGF-β, while the NKT cells can effectively produce INF-y and IL-4. Purpose: To evaluate the role of regulatory T and NKT cells in inflammatory response in septic patients in the first 12 hours of organic dysfunction. Methods: Patients with sepsis will be enrolled in this study. The definition of sepsis will be as follows (Consensus of the 1992, Bones criteria), presence of organic dysfunction with less than 12 hours of evolution with arterial lactate ≥3,0mmol/L. Patients will be divided in two groups: severe sepsis and septic shock. By flow cytometry analyses, the frequence of Tregs and NKT cells will be analyzed in whole blood. The Tregs and NKT cells-associated genes will be quantified by real time PCR (FOXp3 and Vα24/Jα18 transcripts). The cytokine production (TNF-α, INF-γ, IL-2, IL-4, IL-5 and IL-10) will be measured in peripheral blood mononuclear cells supernatants after 72-hour stimulus with anti-CD3 in vitro by the CBA method. The patients will be followed throughout hospital admission. Expected results: Possibly, patients with poor outcomes will present a reduction in Treg numbers or a more pronounced production of Th1 cytokines. This way, we hope that this study finds significant differences in the Tregs and NKT cells expression and in the production of inflammatory cytokines according to the clinical result of patients in the hospital. (AU)