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Massive apoptosis of lymphocytes is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover, sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Thymic output and the numbers of naive and effector/memory CD4+ and CD8+ lymphocytes quickly recovered after sepsis. IL-7 treatment resulted in an accelerated recovery of CD8+ lymphocytes. Next generation sequencing revealed no significant narrowing of the T cell receptor repertoire 3.5 months after sepsis. In contrast, detailed functional analyses of T helper (Th)-cell responses towards a fungal antigen revealed a significant loss of Th cells. Whereas cytokine production was not impaired at the single cell level, the absolute number of Th cells specific for the fungal antigen was reduced. Our data indicate a clinically relevant loss of pathogen-specific T cell clones after sepsis. Given the small number of naive T lymphocytes specific for a given antigen, this decrement of T cell clones remains undetected even by sensitive methods such as deep sequencing. Taken together, our data are compatible with long lasting impairments in CD4+ T-cell responses after sepsis despite rapid recovery of T lymphocyte populations.
This article was published in the following journal.
Name: PloS one
Reconstitution of B-cells after their therapeutic depletion with rituximab mimics the ontogeny of the B-cell linage in patients with rheumatoid arthritis. However, little is known about the effects of...
Although some underpowered studies have proven that increased red blood cell distribution width (RDW) may be associated with short-term prognosis of sepsis, the long-term prognostic value of RDW remai...
Tumor-reactive T cell exhaustion prevents the success of immune therapies. Pegilodecakin activates intratumoral CD8 T cells in mice and induces objective tumor responses in patients. Here we report ...
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Effective vaccines are the cornerstone of our defenses against acute influenza virus infections that result in ∼500 000 annual deaths worldwide. For decades, an on-going concerted effort has been ...
Severe sepsis induces significant changes in expression of insulin- and toll-like receptors, cytokines, markers of apoptosis, and activation of t- and b-lymphocytes.
Sepsis is one of the most common causes of death worldwide. It is caused by a complex of inadequate host responses to infection. Sepsis remains a major challenge of modern intensive care m...
The hypothesis of this study is that bioenergetic failure in human sepsis, related to endocrine, metabolic and mitochondrial dysfunction, is a major determinant of defective host immune re...
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Sepsis is the most common cause of death in the clinical critically ill patients. We have successfully screened the sepsis biomarkers by clinical proteomics approach and found that Vimenti...
A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)
Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.
Wide continuum of associated cognitive and neurobehavioral disorders, including, but not limited to, three core-defining features: impairments in socialization, impairments in verbal and nonverbal communication, and restricted and repetitive patterns of behaviors. (from DSM-V)
Acute neurological dysfunction during severe SEPSIS in the absence of direct brain infection characterized by systemic inflammation and BLOOD BRAIN BARRIER perturbation.
Blood infection that occurs in an infant younger than 90 days old. Early-onset sepsis is seen in the first week of life and most often appears within 24 hours of birth. Late-onset occurs after 1 week and before 3 months of age.
Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections. Sepsis is not just limited to the blood and can affect the whole body, including the organ...