Decreased levels of perforin-positive lymphocytes are associated with posttraumatic complications in patients with major trauma

Hua, Rong; Zhang, Yongmei; Chen, Fuxing; Zhou, Zhonghai; Li, Xi; Shao, Bo-Ming; Wang, Shangjing; Zhang, Yujing; Lv, Xiaoting

doi:10.1016/j.injury.2014.09.011

Cited by 5 publications

(5 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, CD8 + T cells obtained from trauma patients at day 2/3 were characterised by decreased frequencies of granzyme B + cells (figure 4D), consistent with the findings from Hua et al 5. Notably, the CD39 + CD8 + cells from trauma patients displayed features of ‘immune exhaustion’, as reflected by significantly higher proportions of double positive PD-1 + Tim-3 + cells, particularly at day 2/3 (figure 4E).…”

Section: Resultssupporting

confidence: 86%

“…Adaptive immune responses, particularly involving CD8 + T cells, are dysfunctional in patients with major trauma 4 5. Thus, we continued to study the impact of murine liver MT on murine CD8 + T cells in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…Prolonged immune dysfunction is associated with increased susceptibility to secondary infections 2 4. In this regard, previous work has shown that CD8 T cell cytotoxic function is impaired in trauma patients and associated with post-injury multi organ dysfunction syndrome 5. However, the cellular and molecular mechanisms resulting in this immune dysregulation after trauma remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39

Tiwari‐Heckler

Lee

Harbison

et al. 2022

Thorax

View full text Add to dashboard Cite

RationaleThe increased mortality and morbidity seen in critically injured patients appears associated with systemic inflammatory response syndrome (SIRS) and immune dysfunction, which ultimately predisposes to infection. Mitochondria released by injury could generate danger molecules, for example, ATP, which in turn would be rapidly scavenged by ectonucleotidases, expressed on regulatory immune cells.ObjectiveTo determine the association between circulating mitochondria, purinergic signalling and immune dysfunction after trauma.MethodsWe tested the impact of hepatocyte-derived free mitochondria on blood-derived and lung-derived CD8 T cells in vitro and in experimental mouse models in vivo. In parallel, immune phenotypic analyses were conducted on blood-derived CD8 T cells obtained from trauma patients.ResultsIsolated intact mitochondria are functional and generate ATP ex vivo. Extracellular mitochondria perturb CD8+ T cells in co-culture, inducing select features of immune exhaustion in vitro. These effects are modulated by scavenging ATP, modelled by addition of apyrase in vitro. Injection of intact mitochondria into recipient mice markedly upregulates the ectonucleotidase CD39, and other immune checkpoint markers in circulating CD8+ T cells. We note that mice injected with mitochondria, prior to instilling bacteria into the lung, exhibit more severe lung injury, characterised by elevated neutrophil influx and by changes in CD8+ T cell cytotoxic capacity. Importantly, the development of SIRS in injured humans, is likewise associated with disordered purinergic signalling and CD8 T cell dysfunction.ConclusionThese studies in experimental models and in a cohort of trauma patients reveal important associations between extracellular mitochondria, aberrant purinergic signalling and immune dysfunction. These pathogenic factors with immune exhaustion are linked to SIRS and could be targeted therapeutically.

show abstract

Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39

Tiwari‐Heckler

Lee

Harbison

et al. 2022

Thorax

View full text Add to dashboard Cite

show abstract

“…Disorders involving CD8+ T cells can lead to maladaptive immune responses that can cause complications and mortality after severe trauma. Previous studies have found that CD8+ T cell numbers and perforin expression in their granules are lower during the first 24 hours after severe trauma among people experiencing poorer outcomes (MOF and mortality groups), and the trend continues up to day 7 (216)(217)(218). In addition, the frequencies of GrB+ CD8+ T cells in the poorer outcome group are decreased during days 3 to 7 post-trauma (216).…”

Section: Cd8+ T Cellmentioning

confidence: 89%

“…Previous studies have found that CD8+ T cell numbers and perforin expression in their granules are lower during the first 24 hours after severe trauma among people experiencing poorer outcomes (MOF and mortality groups), and the trend continues up to day 7 (216)(217)(218). In addition, the frequencies of GrB+ CD8+ T cells in the poorer outcome group are decreased during days 3 to 7 post-trauma (216). A secondary decrease is observed in week 4 after severe trauma, leading to development of opportunistic infections (217).…”

Section: Cd8+ T Cellmentioning

confidence: 94%

Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities

et al. 2022

View full text Add to dashboard Cite

Although cellular and molecular mediators of the immune system have the potential to be prognostic indicators of disease outcomes, temporal interference between diseases might affect the immune mediators, and make them difficult to predict disease complications. Today one of the most important challenges is predicting the prognosis of COVID-19 in the context of other inflammatory diseases such as traumatic injuries. Many diseases with inflammatory properties are usually polyphasic and the kinetics of inflammatory mediators in various inflammatory diseases might be different. To find the most appropriate evaluation time of immune mediators to accurately predict COVID-19 prognosis in the trauma environment, researchers must investigate and compare cellular and molecular alterations based on their kinetics after the start of COVID-19 symptoms and traumatic injuries. The current review aimed to investigate the similarities and differences of common inflammatory mediators (C-reactive protein, procalcitonin, ferritin, and serum amyloid A), cytokine/chemokine levels (IFNs, IL-1, IL-6, TNF-α, IL-10, and IL-4), and immune cell subtypes (neutrophil, monocyte, Th1, Th2, Th17, Treg and CTL) based on the kinetics between patients with COVID-19 and trauma. The mediators may help us to accurately predict the severity of COVID-19 complications and follow up subsequent clinical interventions. These findings could potentially help in a better understanding of COVID-19 and trauma pathogenesis.

show abstract

Early Diagnosis of Cutaneous Mucormycosis Due to Lichtheimia corymbifera After a Traffic Accident

et al. 2015

View full text Add to dashboard Cite

A case report of cutaneous mucormycosis and obstacles to early diagnosis is presented. A 38-year-old male was involved in a car accident that led to amputation of both lower limbs. Subsequently, he developed fungal wound infection of the left lower limb stump. The infection was detected very early, although the diagnosis was difficult because only a small area was affected and histopathological examination was initially negative. The infection was proven by microscopy, culture and histopathology. The isolate was identified by sequencing of the rDNA ITS region gene (internal transcribed spacer region of ribosomal DNA) as Lichtheimia corymbifera. Liposomal amphotericin B and surgery were successful in management of the disease.

show abstract

Decreased levels of perforin-positive lymphocytes are associated with posttraumatic complications in patients with major trauma

Cited by 5 publications

References 36 publications

Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39

Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39

Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities

Early Diagnosis of Cutaneous Mucormycosis Due to Lichtheimia corymbifera After a Traffic Accident

Contact Info

Product

Resources

About