critical illness , resulting either from infection or from other pro - inflammatory insults , is associated with severe immune dysfunction . however , little is known about how different the dynamics of certain immune ( especially suppressor ) cell populations are depending on the type of primary insult . hein and colleagues   investigated the role of naturally occurring t regulatory ( treg ) cells in 43 patients admitted to the icu with shock due to sepsis and non - sepsis related etiologies . the discriminating feature of the study is that it included most causes of shock , rather than limiting the scope to sepsis . in more detail , the authors compared the absolute numbers , percentages and kinetics of cd4cd25cd127treg cells in 26 critically ill patients with septic shock and 17 patients with cardiogenic , hemorrhagic or toxic shock . naturally occurring cd4cd25treg cells comprise 5 to 10% of cd4 t cells and play a pivotal role in maintaining immunologic homeostasis by inhibiting autoimmunity and controlling inflammation . treg cells express the transcriptional regulator forkhead box p3 ( foxp3 ) , which belongs to the forkhead dna - binding transcription factor family , and is essential for both the development and suppressive function of treg cells . although their exact contribution in sepsis and shock has not been completely elucidated yet , evidence from a number of studies suggests that treg cells act as significant modulators of the innate and adaptive immune response after severe injury . after trauma , treg cell activity increased and was associated with a decreased th1 pro - inflammatory response , potentially contributing to injury - induced immunoparalysis , both in mice and in humans . moreover , in sepsis , not only the percentage of treg cells was higher than in healthy volunteers , but their suppressive activity was enhanced as well , a phenomenon that correlated with increased expression of foxp3 . one explanation for the persistence of treg cells after injury , despite cd4cd25and generalized lymphopenia , may be explained by their greater resistance to apoptosis . therefore , it is not surprising that hein and colleagues   reported that the kinetics of treg cells did not differ significantly between patients with septic and non - sepsis - related shock . interestingly , survivors from the group of patients with septic shock had higher treg cell counts and percentages than non - survivors , which remained consistent at all time points . moreover , higher percentages of treg cells were associated with lower blood arterial lactate and severity of illness score . this could suggest a protective role of treg cells in sepsis , although the study 's small sample size precludes such a conclusion . it is also worth mentioning that this observation is contrary to the results published by monneret and colleagues , where higher percentages of cd4cd25cells were associated with worse prognosis in septic shock . it is always very well received when information extracted from clinical studies is challenged in an experimental model . in the study by hein and colleagues , treg cell percentage increased early after polymicrobial sepsis , but depletion of cd25cells did not affect survival in their model . data on sepsis outcome from previously published studies that used similar antibody depleting strategies have been inconclusive . on the other hand , adoptive transfer of in vitro stimulated treg cells protected mice from lethality in a dose - dependent manner in a polymicrobial sepsis model , and decreased toll - like receptor ( tlr)-2- and tlr-4- mediated pro - inflammatory responses in an experimental burn model . at this point , however , a few important points need to be clarified : first , anti - cd25 antibody treatment may not have completely eliminated cd25/foxp3or cd25/foxp3treg cells ; second , anti - cd25 treatment may also eliminate other activated cells that express cd25 ; and last , it may be useful to investigate whether antibody depletion , if performed later in the course of shock after the pro - inflammatory insult has amplified the regulatory activity of cd4cd25treg cells , could then potentially lead to a different outcome . even if no great variability exists between the kinetics and activity of treg cells in different shock states , the sequence and timing of events that lead to the amplification of their suppressive function certainly need to be studied further .
during the past decade , there have been an increasing number of studies investigating the precise role of t regulatory cells in human disease . first recognized for their ability to prevent autoimmunity , 
 t regulatory cells control effector cd4 + and cd8 + t lymphocytes and innate immune cells by several different suppressive mechanisms , like cell to cell contact , secretion of inhibitory cytokines and cytolysis . 
 this suppressive function of t regulatory cells could contribute in a similar way to the profound immune dysfunction seen in critical illness whether the latter is due to sepsis or severe injury .