CD4FOXP3 T cells and the outcome of patients with severe sepsis and septic shock

• Main Authors: Heng-Ching Huang, 黃恒慶
• Other Authors: Chi-Chang Shieh
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/29740287006471115170

碩士 === 國立成功大學 === 臨床醫學研究所 === 95 === Sepsis, defined as systemic inflammatory response syndrome caused by infection, is a potentially lethal disease in acute hospital setting, killing 20 to 50 percent of severely affected patients. Recent evidences showed that there are two stages. Initially, there is an uncontrolled inflammatory response to invading pathogens; however, there is a shift to an anti-inflammatory response over time. The latter results in the immunoparalysis status and is demonstrated by monocyte deactivation with reduced human leukocyte antigen-DR (HLA-DR) expression. The true mechanism of this shift has not yet been clearly elucidated. Regulatory T cells (Treg), previously characterized by CD4+CD25+, has been recognized to exert a suppression function in T helper lymphocytes and mononuclear phagocytes and play a role in controlling the autoimmunity, tumor immunity and infection inflammation. It has been reported that the number of the peripheral CD4+CD25+ T cells increases in the patient with severe sepsis and septic shock. The role of CD25 as a marker of Treg has recently been replaced by Foxp3, an important transcription factor restricted to the Treg. It has been found that Foxp3 is more specific to the Treg than CD25 and is highly associated with their function. We proposed a hypothesis that CD4+FOXP3+ regulatory T cells, which stood for the functional Treg cells, can influence the outcome of the patients with severe sepsis and septic shock due to their active immunosuppressive function. We performed a one-year prospective observational study in the medical intensive care units in a tertiary teaching hospital in southern Taiwan. Totally, 16 healthy volunteers and 19 patients with severe sepsis and septic shock were recruited in this study. Our results showed that both the percentage of the peripheral CD4+FOXP3+ cells in CD4+ T cells and the absolute number of peripheral CD4+FOXP3+ T cells were depressed at the acute stage of severe sepsis or septic shock in the survival and non-survival patients. In the subacute or recovery stage of the disease course, both the percentage of the peripheral CD4+FOXP3+ cells in CD4+ T cells or the absolute number of peripheral CD4+FOXP3+ T cells recovered gradually in the survival patients. However, this recovery of CD4+FOXP3+ cells was not observed in the non-survival group. TGF-β, which is demonstrated to have a critical role in the development and suppression function of Treg cells, showed a consistent increase with the recovery of the peripheral CD4+FOXP3+ cells in the survival, but not in the non-survival, group. Interestingly, the percentage of the peripheral CD4+CD25+ T cells in CD4+ T cells was in contrary with the results of the CD4+FOXP3+ T cells and TGF-β. This indicates that CD25, previously considered as a specific marker of the natural Treg cell, is not an appropriate marker to predict patient outcome in severe sepsis or septic shock. We also showed that the ratio of peripheral CD4 to CD8 T cells gradually rose in the non-survival patients but stayed stable in the survival patients. Furthermore, the balance of peripheral Th2 cells to Th1 T cells did not change significantly in patients. There was no linear association between the percentage of the peripheral CD4+FOXP3+ cells in CD4+ T cells and the ratio of Th2/Th1 T cells or that of CD4/CD8 in lymphocytes. Our results showed that the ratio of CD4+FOXP3+ T cells in peripheral CD4+ T cells or the absolute number of peripheral CD4+FOXP3+ cells of the patients with severe sepsis and septic shock is a good predictor of the patients’ outcomes. In severe sepsis or septic shock, Treg may play a beneficial role to reverse the uncontrolled inflammation. The increase of Treg hence may foretell the recovery in these patients, rather than immunoparalysis as previously surmised.