Sepsis syndrome (also known as systemic inflammatory response associated with infection,  sepsis, severe sepsis, and septic shock) is a condition characterized by a whole-body inflammatory  state and the presence of a known or suspected bacteria, usually gram-negative organisms. The  condition is a common problem in all age groups and is a leading cause of mortality in intensive care  units, particularly in children and older adults. Although sepsis causes a marked depletion of  lymphocytes, the function of different lymphocyte subsets in pathogenesis (protection or  exacerbation) of septic shock is unclear. Interestingly, recent reports show that one subset of T  lymphocytes that co-express CD4, CD25, Foxp3 molecules (collectively known as regulatory T cells)  is increased in sepsis. We have observed similar increase in percentages of Tregs in a laboratory  model of the sepsis.    We hypothesize that Tregs play important role in the pathogenesis of sepsis/septic shock. Indeed,  we have found that depletion of Treg cells (by anti-CD25 mAb treatment) leads to enhanced  sensitivity to LPS resulting in acute death within 3-5 hr in an otherwise non-lethal challenge.  Interestingly, further preliminary studies indicate CD4+ T cells may not be involved in this process,  suggesting that depletion of conventional Tregs (which are CD4+CD25+Foxp3+) may not be  responsible for enhanced the susceptibility to LPS following anti-CD25 mAb treatment. Our goal is  to understand how CD25+ cells ameliorate lethality associated with LPS-induced septic  shock. We aim to determine whether the effects anti-CD25 mAb in enhancing sensitivity to LPS are  mediated by depletion of other CD25-bearing cells such as B cells, CD8+, NKT and T cells,  monocytes that may negatively regulate LPS signaling. Additionally, using molecular approaches we  will investigate key molecules in involved in LPS signaling (including MyD88, STATS, SOCS, TRIF  etc) to determine whether binding of anti-CD25 mAb to target cells enhances their activities in vitro.    Sepsis syndrome and septic shock are common and frequently fatal clinical conditions in all age  groups and are leading cause of mortality in intensive care units, particularly in children and older  adults. Therefore, understanding the pathogenesis of the disease is an important step towards  designing appropriate clinical interventions both for preventive and treatment purposes. The results  obtained from these studies would enhance our understanding of the pathophysiology of  sepsis/septic shock and could provide possible therapeutic targets for clinical management of the  condition. G neg. Bacteria in Blood © copyright 2011