An increased alveolar CD4 + CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality

Adamzik, Michael; Bröll, J.; Steinmann, Jörg; Westendorf, Astrid M.; Rehfeld, Irene; Kreissig, Carla; Peters, Jürgen

doi:10.1007/s00134-013-3036-3

Cited by 72 publications

(88 citation statements)

References 28 publications

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“…These authors also showed a higher mortality rate using T-regs knockout mice, due to persistent lung inflammation. Recently, a clinical study from Germany showed an increase in the T-cell subset ratio only, i.e., an augmentation of T-regulator cells/all CD4 T-cells, in 47 ARDS patients compared to eight controls requiring abdominal surgery for cancer [31]. Similar trends were observed in our study, without reaching significance (p=0.11, data not shown).…”

Section: Discussionsupporting

confidence: 65%

Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells

Risso

Kumar

Ticchioni

et al. 2015

Eur J Clin Microbiol Infect Dis

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Acute respiratory distress syndrome (ARDS) in humans is characterized by the infiltration of polymorphonuclears in the alveolar spaces. However, the role of T-cells in ARDS is unknown. Our aim was to characterize the T-cell phenotype in bronchoalveolar lavage (BAL) during the early phase of acute lung infection(ALI)/ARDS-infected patients in comparison to a control group (CG). BAL lymphocyte phenotypes of two ALI, 16 ARDS, and eight CG were examined by flow cytometry. ALI/ARDS showed a significant increase in CD4 and CD8 T-cell activation as compared to CG. Moreover, a significant level of proliferation was observed using the Ki67 marker in ARDS patients as compared to controls (median): 37 versus 6 % for CD4 T-cells (p = 0.022) and 34 versus 2 % for CD8 T-cells (p = 0.009). In contrast, the percentage of T-regulatory cells and apoptotic T-cells were similar in both groups. Among costimulatory molecules, we observed an overexpression of CTLA-4/CD152 on CD4 T-cells in ALI/ARDS as compared to CG: 30 versus 7 %, respectively (p = 0.063). In further characterizing T-cell subsets expressing high levels of CD152, we found the presence of IL-17 secreting CD4 T-cells in ALI/ARDS. In humans, ALI/ARDS due to infection is associated with a high level of T-cell activation and proliferation, along with the presence of Th17 cells, which are known to attract polymorphonuclears.

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Section: Discussionsupporting

confidence: 65%

Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells

Risso

Kumar

Ticchioni

et al. 2015

Eur J Clin Microbiol Infect Dis

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show abstract

“…Additionally, a deficiency of CD4+ CD25+ FoxP3+ T regulatory cells has been suggested to be a first-hit risk factor for TRALI, using a murine model of antibody-mediated TRALI [13]. In contrast, alveolar CD4+ CD25+ FoxP3+ T regulatory cells were reported to be increased in ARDS patients, with a concomitant correlation with increased IL-10 levels [74]. It will be important to more firmly establish the role T regulatory cells and IL-10 in both ARDS and TRALI.…”

Section: Discussionmentioning

confidence: 99%

The Pathogenic Involvement of Neutrophils in Acute Respiratory Distress Syndrome and Transfusion-Related Acute Lung Injury

Rebetz

Semple

Kapur

2018

Transfus Med Hemother

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The acute respiratory distress syndrome (ARDS) is a serious and common complication of multiple medical and surgical interventions, with sepsis, pneumonia, and aspiration of gastric contents being common risk factors. ARDS develops within 1 week of a known clinical insult or presents with new/worsening respiratory symptoms if the clinical insult is unknown. Approximately 40% of the ARDS cases have a fatal outcome. Transfusion-related acute lung injury (TRALI), on the other hand, is characterized by the occurrence of respiratory distress and acute lung injury, which presents within 6 h after administration of a blood transfusion. In contrast to ARDS, acute lung injury in TRALI is not attributable to another risk factor for acute lung injury. ‘Possible TRALI', however, may have a clear temporal relationship to an alternative risk factor for acute lung injury. Risk factors for TRALI include chronic alcohol abuse and systemic inflammation. TRALI is the leading cause of transfusion-related fatalities. There are no specific therapies available for ARDS or TRALI as both have a complex and incompletely understood pathogenesis. Neutrophils (polymorphonuclear leukocytes; PMNs) have been suggested to be key effector cells in the pathogenesis of both syndromes. In the present paper, we summarize the literature with regard to PMN involvement in the pathogenesis of both ARDS and TRALI based on both human data as well as on animal models. The evidence generally supports a strong role for PMNs in both ARDS and TRALI. More research is required to shed light on the pathogenesis of these respiratory syndromes and to more thoroughly establish the nature of the PMN involvement, especially considering the heterogeneous etiologies of ARDS.

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“…70,71 Given their limited numbers, Tregs have been shown to become highly proliferative after lung inflammation and are a key feature in controlling exuberant immune responses. 65,72 Ongoing clinical trials are evaluating the role of Tregs in solid-organ transplantation. 73 Studies by Neujahr et al and Bhorade et al have shown that a decreased proportion of Foxp3 + cells among CD4 cells in bronchoalveolar lavage (BAL) can potentially predict worse lung allograft outcome and help guide therapeutic immunosuppression in lung transplant recipients.…”

Section: Resolution and Repair Mechanismsmentioning

confidence: 99%

Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Mechanisms: A 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation

Gelman

Fisher

Huang

et al. 2017

The Journal of Heart and Lung Transplantation

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An increased alveolar CD4 + CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality

Abstract: An increased T-regulatory cell ratio in the admission BAL of patients with ARDS is an important and independent risk factor for 30-day mortality.

Cited by 72 publications

References 28 publications

Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells

Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells

The Pathogenic Involvement of Neutrophils in Acute Respiratory Distress Syndrome and Transfusion-Related Acute Lung Injury

Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Mechanisms: A 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation

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