Removal of increased circulating CD4+CD25+Foxp3+ regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers

Ono, Satoshi; Kimura, Akifumi; Hiraki, Shuichi; Takahata, Risa; Tsujimoto, Hironori; Kinoshita, Manabu; Miyazaki, Hiromi; Yamamoto, Junji; Hase, Kazuo; Saitoh, Daizoh

doi:10.1016/j.surg.2012.06.023

Cited by 38 publications

(28 citation statements)

References 31 publications

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“…In consistence, similar increase in Treg frequency has also been reported in the periphery of septic patients [45–47], which was shown to be a result of the decreased effector populations of CD4 + T cells and resistance of Tregs to sepsis-induced apoptosis [48]. However, the role of Tregs in sepsis is still argued as increased Tregs have been accounted for decreased survival [49] as well as improved recovery [50,51]. In this study we also demonstrate a considerable decrease in the absolute cell numbers of naïve and Tcm subsets of splenic CD4 + T cells 20 h after CLP, with Tcm cell numbers being highly reduced in particular.…”

Section: Discussionmentioning

confidence: 61%

Differential alterations of tissue T-cell subsets after sepsis

et al. 2015

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Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20 h later. Total lymphocyte count showed a significant reduction in septic thymus, spleen and blood but not in lungs and liver. The septic thymi were hypocellular with severe reduction in cell numbers of immature CD4+CD8+ subset. CD4+ T and CD8+ T lymphocyte numbers in septic spleens were also significantly reduced, but the frequency of CD4+CD25+ Tregs was significantly increased. In addition, naïve and Tcm CD4+ T cell numbers were significantly reduced in the septic spleens. By contrast, in septic liver the CD8+ T cell numbers were significantly increased, whereas NKT cell numbers were reduced, but more activated with increased CD69 and CD25 expression. In the septic lungs, the CD4+ T and CD8+ T cell numbers showed no significant change, whereas they were severely reduced in the septic blood. Overall, this study provides important information on the alterations of different T-cell subsets in various tissues after sepsis.

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Section: Discussionmentioning

confidence: 61%

Differential alterations of tissue T-cell subsets after sepsis

et al. 2015

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“…Despite these findings, the role of T reg in septic injury is still debated. Excessive T reg formation decreases survival in animal models of sepsis [130], as well as improving outcomes and immunity [131][132][133]. These contrasting results, particularly in human studies, may be related to the sensitivity of analyzing FoxP3 expression via flow cytometry, the timing of analysis, and the ability to discern the methylation status of the FoxP3 promoter in circulating septic lymphocytes [134].…”

Section: Increases In T Reg Frequency And/or Functionmentioning

confidence: 99%

Impact of sepsis on CD4 T cell immunity

Cabrera-Pérez¹,

Condotta

Badovinac

et al. 2014

Journal of Leukocyte Biology

154

124

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Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state.

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“…In a study by Gomez et al [50], patients with sepsis at admission possessed a high percentage of apoptotic CD4 T cells and CD8 T cells, in addition to high levels of both pro-and anti-inflammatory cytokines. Ono et al [51] found a substantial increase in the percentage of Treg cells among the circulating peripheral CD4+ T cells in patients with septic shock. Another study showed that the percentages of Tregs in peripheral blood lymphocytes were significantly increased in patients with sepsis, and there was a significantly positive correlation between serum IL-10 levels and the percentage of Tregs in septic mice 3 days after CLP [52].…”

Section: Discussionmentioning

confidence: 97%

The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice

et al. 2015

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Septic encephalopathy represents the most frequently observed form of encephalopathy in intensive care units. Interactions between the immune and nervous systems have been observed in experimental sepsis. Therefore, the aim of the current study was to characterize the effect of different severities of sepsis on encephalopathy and the inflammatory profile of the spleen. We hypothesized that different grades of sepsis severity would lead to variations in encephalopathy and activation of spleen cells. We induced sepsis of different severities in Balb/c mice by cecal ligature and puncture (CLP). Six and 12 h after CLP induction, behavioral impairment was assessed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) test. The animals were then killed, and the plasma, spleen, and hippocampus were removed. Levels of the encephalopathy marker S100β were measured in plasma. Spleens were weighed and then a characterization of splenic lymphocytes was performed by flow cytometry (cytotoxic T lymphocyte, T helper lymphocytes, B lymphocytes, T regulatory cells, and Th17 cells). Cytokine levels in the spleen and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA), and cytokine levels in plasma were performed with MilliPlex® technology. Our results showed that behavioral impairment as measured by the SHIRPA test and elevation in plasma S100β levels were significant in moderate and severe CLP groups compared to those in the sham control group. Regarding immunological alterations, we were unable to observe changes in the weights of the spleen and the profile of lymphocytes 6 h after CLP. However, several cytokines, including IL-6, IL-10, and IL-1β, were increased in spleen and plasma. In conclusion, we observed variations in encephalopathy as measured by plasma S100β, which were mediated by the severity of sepsis; however, we did not observe a different activation of spleen cells 6 h post-CLP, despite evidence of inflammation. Taken together, our data indicate that the severity of sepsis impacts the brain in absence of a change in the spleen lymphocyte profile.

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Removal of increased circulating CD4+CD25+Foxp3+ regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers

Cited by 38 publications

References 31 publications

Differential alterations of tissue T-cell subsets after sepsis

Differential alterations of tissue T-cell subsets after sepsis

Impact of sepsis on CD4 T cell immunity

The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice

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