Abstract
IntroductionAlthough regulatory T lymphocytes (Tregs) have a pivotal role in preventing autoimmune diseases and limiting chronic inflammatory conditions, they may also block beneficial immune responses by preventing sterilizing immunity to certain pathogens.MethodsTo determine whether naturally occurring Treg cells have a role in inflammatory response and outcome during shock state we conducted an observational study in two adult ICUs from a university hospital. Within 12 hours of admission, peripheral whole blood was collected for the measurement of cytokines and determination of lymphocyte count. Sampling was repeated at day three, five and seven. Furthermore, an experimental septic shock was induced in adult Balb/c mice through caecal ligation and puncture.ResultsForty-three patients suffering from shock (26 septic, 17 non septic), and 7 healthy volunteers were included. The percentage of Tregs increased as early as 3 days after the onset of shock, while their absolute number remained lower than in healthy volunteers. A similar pattern of Tregs kinetics was found in infected and non infected patients. Though there was an inverse correlation between severity scores and Tregs percentage, the time course of Tregs was similar between survivors and non survivors. No relation between Tregs and cytokine concentration was found. In septic mice, although there was a rapid increase in Treg cells subset among splenocytes, antibody-induced depletion of Tregs before the onset of sepsis did not alter survival.ConclusionsThese data argue against a determinant role of Tregs in inflammatory response and outcome during shock states.
Highlights
Regulatory T lymphocytes (Tregs) have a pivotal role in preventing autoimmune diseases and limiting chronic inflammatory conditions, they may block beneficial immune responses by preventing sterilizing immunity to certain pathogens
Several groups have implicated an active lymphoid suppressor cell population: the naturally occurring regulatory T cells (Tregs) [5,6]. These CD4+CD25+ cells make up only a small fraction of the T-lymphocyte population, they are potent inhibitors of immune response [7], and are widely regarded as the primary mediators of peripheral tolerance, able to maintain immune homeostasis, to prevent autoimmunity, and to modulate inflammation induced by pathogens and environmental insults [5]
Comparisons between patients with septic shock, patients with non-septic shock and/or healthy volunteers were performed by using Student’s t test as normally distributed values (Kolmogoroff-Smirnov test), Mann-Whitney U test, or Results From January to June 2007, 43 consecutive patients suffering from shock were included
Summary
Regulatory T lymphocytes (Tregs) have a pivotal role in preventing autoimmune diseases and limiting chronic inflammatory conditions, they may block beneficial immune responses by preventing sterilizing immunity to certain pathogens. Sepsis syndrome remains the most common cause of mortality in ICUs, causing about 750,000 deaths annually in the USA [1,2]. Several groups have implicated an active lymphoid suppressor cell population: the naturally occurring regulatory T cells (Tregs) [5,6]. These CD4+CD25+ cells make up only a small fraction of the T-lymphocyte population, they are potent inhibitors of immune response [7], and are widely regarded as the primary mediators of peripheral tolerance, able to maintain immune homeostasis, to prevent autoimmunity, and to modulate inflammation induced by pathogens and environmental insults [5]
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