Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with chronic renal failure on hemodialysis treatment

Konno, Osamu; Hirano, Toshihiko; Katsuyama, Kanako; Oka, Kitaro; Matsuno, Naoto; Nagao, Toshiyasu

doi:10.1016/j.trim.2006.10.003

Cited by 5 publications

(5 citation statements)

References 23 publications

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“…In our previous study including 18 CRF patients, (18) we reported that the suppressive efficacies of glucocorticoids and calcineurin inhibitors evaluated in PBMCs stimulated with TSST-1 were lower than those evaluated in concanavalin A-stimulated PBMCs, which was supported from the present study. We have also compared the amounts of interferon-γ and IL-4 produced in culture media between concanavalin A-and TSST-1-stimulated PBMCs, but no significant difference was found, and thus the molecular background of the decreased drug sensitivity in TSST-1-stimulated PBMCs remains to be elucidated.…”

Section: Discussionsupporting

confidence: 87%

“…In our preliminary study, (18) we reported that the suppressive efficacies of glucocorticoids and calcineurin inhibitors evaluated in PBMCs stimulated with an S. aureus-derived superantigen TSST-1 were lower than those evaluated in concanavalin A-stimulated PBMCs. However, the molecular background of the decreased drug sensitivity in TSST-1-stimulated PBMCs of CRF patients remains to be elucidated.…”

Section: Introductionmentioning

confidence: 78%

“…We have also compared the amounts of interferon-γ and IL-4 produced in culture media between concanavalin A-and TSST-1-stimulated PBMCs, but no significant difference was found, and thus the molecular background of the decreased drug sensitivity in TSST-1-stimulated PBMCs remains to be elucidated. (18) As such, it would be informative to compare several other cytokine levels in culture supernatant of patients' PBMCs stimulated with TSST-1 with those in culture supernatant of PBMCs stimulated with concanavalin A. We have reported, in an assay procedure using healthy PBMCs, that TSST-1 stimulation significantly promoted IL-2 production, as compared to concanavalin A stimulation.…”

Section: Discussionmentioning

confidence: 99%

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Influence of Bacterial Superantigen TSST-1 Against the Anti-Proliferative Efficacy of Immunosuppressive Drugs and Interleukin 2 Production in Peripheral Blood Mononuclear Cells of Hemodialysis Patients and Healthy Subjects

Taira

Katsuyama

Konno

et al. 2008

Immunopharmacology and Immunotoxicology

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We investigated the influence of bacterial superantigen on the efficacies of immunosuppressive drugs on the blastogenesis of peripheral-blood mononuclear cells of 27 hemodialysis patients awaiting renal transplantation. The IC 50 values for prednisolone, methylprednisolone, cyclosporine, and tacrolimus evaluated in the superantigenstimulated cells were significantly higher than those evaluated in concanavalin A-stimulated cells (p = 0.0002-0.018). Interleukin-2 amounts produced from superantigen-stimulated cells were significantly larger than those from concanavalin A-stimulated cells (p = 0.0363). These results suggest that superantigen attenuates the suppressive efficacies of glucocorticoids and calcineurin inhibitors by stimulating lymphocytes of hemodialysis patients awaiting transplantation to overproduce interleukin-2.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of Bacterial Superantigen TSST-1 Against the Anti-Proliferative Efficacy of Immunosuppressive Drugs and Interleukin 2 Production in Peripheral Blood Mononuclear Cells of Hemodialysis Patients and Healthy Subjects

Taira

Katsuyama

Konno

et al. 2008

Immunopharmacology and Immunotoxicology

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“…Therefore, we selected 20 and 200 μM (10 X of 20 μM) and assessed the changes in the expression of activation markers on the lymphocytes after T cell stimulation using FCM. As superantigen stimulation induces T cell activation in the presence of GC ( 37 , 45 ), we stimulated PBMCs with TSST-1 in the presence of P4 and/or COR and analyzed the expression of CD25 and PD-1 after 72 h.…”

Section: Resultsmentioning

confidence: 99%

High-progesterone environment preserves T cell competency by evading glucocorticoid effects on immune regulation

et al. 2022

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Progesterone (P4) and glucocorticoid (GC) play crucial roles in the immunoregulation of a mother to accept and maintain a semi-allogenic fetus. P4 concentration increases during pregnancy and becomes much higher in the placenta than in the other peripheral tissues, wherein the concentration of cortisol (COR), the most abundant GC and a strong immunosuppressor, remains uniform throughout the rest of the body. Here, we evaluated the effect of a high-P4 environment on pregnant immunity by comparing it with COR. Naïve T cell proportion increased transiently in peripheral blood of pregnant women just after delivery and decreased after one month. T cells stimulated with superantigen toxic-shock-syndrome-1 (TSST-1) in the presence of P4 stayed in the naïve state and did not increase, irrespective of the presence of COR, and reactive T cells could not survive. Treatment of T cells with P4 without T cell receptor (TCR) stimulation transiently suppressed T cell activation and proliferation, whereas the levels remain unaltered if P4 was not given before stimulation. Comparison of the engraftment and response against specific antigens using hu-PBL-NOG-hIL-4-Tg mice showed that P4-pretreated lymphocytes preserved CD62L expression and engrafted effectively in the spleen. Moreover, they produced antigen-specific antibodies, whereas COR-pretreated lymphocytes did not. These results suggest that a high-P4 environment suppresses T cell activation and induces T cell migration into lymphoid tissues, where they maintain the ability to produce anti-pathogen antibodies, whereas COR does not preserve T cell function. The mechanism may be pivotal in maintaining non-fetus-specific T cell function in pregnancy.

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“…Both SEB and Tsst owing to their virulence potential, qualify as biowarfare molecules [8][9][10]. In the event of biological emergency, the disease is likely to be confused with naturally occurring epidemic, further confounded by difficulties for the timely diagnosis which could lead to delay in the initiation of treatment or control procedures.…”

Section: Introductionmentioning

confidence: 99%

Application of a Chimeric Protein Construct having Enterotoxin B and Toxic Shock Syndrome Toxin Domains of S. aureus in Immunodiagnostics

et al. 2012

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Staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 are the super antigens responsible for diseases such as staphylococcal food poisoning and toxic shock syndrome. At low serum concentrations, SEB can trigger toxic shock, profound hypotension and multi organ failure and hence is recognized as biowarfare molecule. In this study, a multidomain fusion protein (r-TE) was generated with specificity for SEB and toxic shock syndrome toxin (Tsst-1). The fusion gene comprising the conserved regions of seb and the tsst genes was codonoptimized for expression in Escherichia coli and encoded a 26 kDa recombinant multidomain chimeric protein (r-TE). Hyperimmune antiserum raised against r-TE specifically reacted with SEB (*28 kDa) and Tsst-1 (*22 kDa) components during Western blot analysis and by plate ELISA in confirmed toxin producing strains of S. aureus. The antigenicity of the SEB component of the r-TE protein was also confirmed using TECRA kit. The described procedure of creating a single protein molecule carrying components of two different toxins whilst still retaining the original antigenic determinants of individual toxins proved highly advantageous in the development of rapid, reliable and cost effective immunoassays and may also have the potential to serve as candidate molecule for vaccine studies.

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Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with chronic renal failure on hemodialysis treatment

Cited by 5 publications

References 23 publications

Influence of Bacterial Superantigen TSST-1 Against the Anti-Proliferative Efficacy of Immunosuppressive Drugs and Interleukin 2 Production in Peripheral Blood Mononuclear Cells of Hemodialysis Patients and Healthy Subjects

Influence of Bacterial Superantigen TSST-1 Against the Anti-Proliferative Efficacy of Immunosuppressive Drugs and Interleukin 2 Production in Peripheral Blood Mononuclear Cells of Hemodialysis Patients and Healthy Subjects

High-progesterone environment preserves T cell competency by evading glucocorticoid effects on immune regulation

Application of a Chimeric Protein Construct having Enterotoxin B and Toxic Shock Syndrome Toxin Domains of S. aureus in Immunodiagnostics

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