Analysis of the early response to TSST-1 reveals Vβ-unrestricted extravasation, compartmentalization of the response, and unresponsiveness but not anergy to TSST-1

Waclavicek, Martina; Stich, Norbert; Rappan, Ingrid; Bergmeister, Helga; Eibl, Martha M.

doi:10.1189/jlb.0108074

Cited by 13 publications

(28 citation statements)

References 44 publications

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“…A transient leukopenia has occasionally been observed, which was attributed to neutrophil sequestration in lymph nodes and spleen [32]. Biochemical analysis will demonstrate multiorgan injury and may show increased urea and creatinine concentrations, elevated hepatic transaminases and bilirubin, hypoalbuminemia, and abnormal electrolyte concentrations.…”

Section: Clinical Features Investigations and Diagnosismentioning

confidence: 95%

Staphylococcal Toxic Shock Syndrome: Mechanisms and Management

Silversides

Lappin

Ferguson

2010

Curr Infect Dis Rep

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Staphylococcal toxic shock syndrome is a rare complication of Staphylococcus aureus infection in which bacterial toxins act as superantigens, activating very large numbers of T cells and generating an overwhelming immune-mediated cytokine avalanche that manifests clinically as fever, rash, shock, and rapidly progressive multiple organ failure, often in young, previously healthy patients. The syndrome can occur with any site of S. aureus infection, and so clinicians of all medical specialties should have a firm grasp of the presentation and management. In this article, we review the literature on the pathophysiology, clinical features, and treatment of this serious condition with emphasis on recent insights into pathophysiology and on information of relevance to the practicing clinician.

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Section: Clinical Features Investigations and Diagnosismentioning

confidence: 95%

Staphylococcal Toxic Shock Syndrome: Mechanisms and Management

Silversides

Lappin

Ferguson

2010

Curr Infect Dis Rep

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“…Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood of healthy human adults using density gradient centrifugation with Lymphoprep™ (Axis-Shield PoC, Oslo, Norway) as previously described [34]. PBMC were cultured in complete medium (RPMI 1640 medium (Gibco), 10% FCS (HyClone, Logan, UK), 2 mM L-glutamine (Invitrogen, Paisley, UK), 100 U/mL penicillin, and 100 µg/mL streptomycin (Invitrogen)) at a concentration of 5 × 10 6 /mL in 24-well flat-bottom tissue culture plates (Sarstedt, Newton, NC, USA) and stimulated with a final concentration of 1 ng/mL recombinant TSST-1 wildtyp (rTSST-1 wt) in humidified atmosphere (37 °C, 5% CO 2 ) for time periods indicated in the text.…”

Section: Methodsmentioning

confidence: 99%

“…Primer pairs were synthesized at MWG/Eurofins Biotech (Heidelberg, Germany) and at Invitrogen. cDNA standards were prepared as previously described [34]. The primer sequences used for amplification of human cytokine cDNAs by real-time PCR were as follows:…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure

Stich

Model

Samstag³

et al. 2014

Toxins

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Toxic shock syndrome (TSS) results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs). There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days) lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1) neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation), determination of IL-2 release in the cell supernatant (ELISA), and IL-2 gene activation (real-time PCR (RT-PCR)). Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure.

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“…In our lab, in 2002, two amino acids were exchanged (G31R and H135A), which led to inhibition of both binding to MHC class II and T cell receptor molecules [18]. Safety, tolerability, and immunogenicity were extensively tested in vitro in human blood mononuclear cells, and in vivo in rabbits and mice [18][19][20]. It was then decided to start a randomized, double-blind, adjuvant-controlled, doseescalation first-in-man trial in a healthy population in Austria.…”

mentioning

confidence: 99%