Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome

2009 ◽  
Vol 15 (6) ◽  
pp. 641-648 ◽  
Author(s):  
Thu A Chau ◽  
Michelle L McCully ◽  
William Brintnell ◽  
Gary An ◽  
Katherine J Kasper ◽  
...  
Keyword(s):  
Cell Wall ◽  
T Cell ◽  
T Cell Activation ◽  
Toxic Shock Syndrome ◽  
Cell Activation ◽  
Toll Like Receptor ◽  
Toxic Shock ◽  
Toll Like Receptor 2

scholarly journals Protection against lethal toxic shock by targeted disruption of the CD28 gene.

1996 ◽  
Vol 183 (6) ◽  
pp. 2675-2680 ◽  
Author(s):  
B Saha ◽  
D M Harlan ◽  
K P Lee ◽  
C H June ◽  
R Abe
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Toxic Shock Syndrome ◽  
Cell Activation ◽  
Dose Effect ◽  
Tnf Alpha ◽  
Toxic Shock ◽  
Costimulatory Signals ◽  
Toxigenic Strains

Toxic shock syndrome (TSS) is a multi system disorder resulting from superantigen-mediated cytokine production. Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus. It is clearly established that besides antigen-specific signals a variety of costimulatory signals are required for full T cell activation. However, the nature and potential redundancy of costimulatory signals are incompletely understood, particularly with regards to superantigen-mediated T cell activation in vivo. Here we report that CD28-deficient mice (CD28-/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+/-) littermate mice were partially resistant to TSST-1. The mechanism for the resistance of the CD28 (-/-) mice was a complete abrogation of TNF-alpha accumulation in the serum and a nearly complete (90%) impairment of IFN-gamma secretion in response to TSST-1 injection. In contrast, the serum level of IL-2 was only moderately influenced by the variation of CD28 expression. CD28 (-/-) mice retained sensitivity to TNF-alpha as demonstrated by equivalent lethality after cytokine injection. These findings establish an essential requirement for CD28 costimulatory signals in TSST-1-induced TSS. The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+/+), CD28 heterozygous (CD28+/-), and CD28-/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation. Finally, as these results demonstrate the primary and non-redundant role of CD28 receptors in the initiation of the in vivo cytokine cascade, they suggest therapeutic approaches for superantigen-mediated immunopathology.

scholarly journals Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

2021 ◽  
Author(s):  
Marion Moreews ◽  
Kenz Le Gouge ◽  
Alicia Bellomo ◽  
Christophe Malcus ◽  
Rémi Pescarmona ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Kawasaki Disease ◽  
T Cell Activation ◽  
Toxic Shock Syndrome ◽  
Healthy Children ◽  
Toxic Shock ◽  
Hla Dr ◽  
Inflammatory Syndrome

AbstractObjectivesMultiple Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of COVID-19 and occurs in previously healthy children. MIS-C combines features of Kawasaki disease and Toxic Shock Syndrome (TSS).MethodsChildren with suspected MIS-C were included within the first week of diagnosis and a large scale immunoassay was performed to determein the immunologic signature of these patients.ResultsWe characterized the immunological profile of 27 MIS-C cases in comparison with 4 KD and 4 TSS cases. Similarly to TSS, an increase of serum inflammatory cytokines (IL-6, TNF-a, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR monocytes, a feature often associated with immune paralysis. Expansions of T cells expressing the Vβ21.3 T cell receptor β chain variable region were detected in both CD4 and CD8 subsets in almost 50% of patients and Vβ21.3-positive T cells expressed high level of HLA-DR highlighting their specific activation. TCR sequencing uncovered the polyclonal nature of the Vβ 21.3+ population. SARS-CoV2 antigene-specific production of interferon gamma in T cells was not increased in MIS-C T cells compared to COVID-19 patients suggesting the antigen-specific immune response in MIS-C patients is not pivotal to the manifestation.ConclusionsOur findings argue in favor of a strong activation of the immune system related to a superantigenic immune response in MIS-C with a specific polyclonal Vβ21.3 T cell expansion.Key messagesWhat is already known about this subject ?MIS-C occurs 3-5 weeks after acute SARS-CoV2 infection and overlap features of Toxic Shock syndrome and Kawasaki disease.MIS-C appears different in term of cytokine and autoantibodies generation from KD with subtle signs of T cells activationWhat does this study add?This study demonstrates that Vβ21.3+ CD4 and CD8 T cells are highly increased in about 50% of MIS-C and distinctive of the Vβ2+ expansion observed in toxic shock syndrome in This reflects a specific T cell activation and cytokine release syndrome similar to toxic shock syndromeHow mich this impact on clinical practice or future developments?Vβ21.3+ signature can be available on a short term basis by flowcytometry and represents a signature of the MIS-C.As for TSS, immunomodulating therapies may revert the superantigenic activation and resolve this life threatening pediatric condition.

scholarly journals Interleukin-7 and Toll-Like Receptor 7 Induce Synergistic B Cell and T Cell Activation

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94756 ◽  
Author(s):  
Angela Bikker ◽  
Aike A. Kruize ◽  
Kim M. G. van der Wurff-Jacobs ◽  
Rogier P. Peters ◽  
Marije Kleinjan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Toll Like Receptor ◽  
Interleukin 7

scholarly journals Expression of the Receptor Tyrosine Kinase EphB2 on Dendritic Cells Is Modulated by Toll-Like Receptor Ligation but Is Not Required for T Cell Activation

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0138835 ◽  
Author(s):  
Patrice N. Mimche ◽  
Lauren M. Brady ◽  
Shirley Keeton ◽  
David S. J. Fenne ◽  
Thayer P. King ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Activation ◽  
Receptor Tyrosine Kinase ◽  
Cell Activation ◽  
Toll Like Receptor ◽  
Receptor Ligation
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