29 research outputs found

    Streptococcus pneumoniae Serotype 1 Capsular Polysaccharide Induces CD8+CD28βˆ’ Regulatory T Lymphocytes by TCR Crosslinking

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    Zwitterionic capsular polysaccharides (ZPS) of commensal bacteria are characterized by having both positive and negative charged substituents on each repeating unit of a highly repetitive structure that has an Ξ±-helix configuration. In this paper we look at the immune response of CD8+ T cells to ZPSs. Intraperitoneal application of the ZPS Sp1 from Streptococcus pneumoniae serotype 1 induces CD8+CD28βˆ’ T cells in the spleen and peritoneal cavity of WT mice. However, chemically modified Sp1 (mSp1) without the positive charge and resembling common negatively charged polysaccharides fails to induce CD8+CD28βˆ’ T lymphocytes. The Sp1-induced CD8+CD28βˆ’ T lymphocytes are CD122lowCTLA-4+CD39+. They synthesize IL-10 and TGF-Ξ². The Sp1-induced CD8+CD28βˆ’ T cells exhibit immunosuppressive properties on CD4+ T cells in vivo and in vitro. Experimental approaches to elucidate the mechanism of CD8+ T cell activation by Sp1 demonstrate in a dimeric MHC class I-Ig model that Sp1 induces CD8+ T cell activation by enhancing crosslinking of TCR. The expansion of CD8+CD28βˆ’ T cells is independent, of direct antigen-presenting cell/T cell contact and, to the specificity of the T cell receptor (TCR). In CD8+CD28βˆ’ T cells, Sp1 enhances Zap-70 phosphorylation and increasingly involves NF-ΞΊB which ultimately results in protection versus apoptosis and cell death and promotes survival and accumulation of the CD8+CD28βˆ’ population. This is the first description of a naturally occurring bacterial antigen that is able to induce suppressive CD8+CD28βˆ’ T lymphocytes in vivo and in vitro. The underlying mechanism of CD8+ T cell activation appears to rely on enhanced TCR crosslinking. The data provides evidence that ZPS of commensal bacteria play an important role in peripheral tolerance mechanisms and the maintenance of the homeostasis of the immune system

    A systematic review of outcome and outcome-measure reporting in randomised trials evaluating surgical interventions for anterior-compartment vaginal prolapse: a call to action to develop a core outcome set

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    INTRODUCTION: We assessed outcome and outcome-measure reporting in randomised controlled trials evaluating surgical interventions for anterior-compartment vaginal prolapse and explored the relationships between outcome reporting quality with journal impact factor, year of publication, and methodological quality. METHODS: We searched the bibliographical databases from inception to October 2017. Two researchers independently selected studies and assessed study characteristics, methodological quality (Jadad criteria; range 1-5), and outcome reporting quality Management of Otitis Media with Effusion in Cleft Palate (MOMENT) criteria; range 1-6], and extracted relevant data. We used a multivariate linear regression to assess associations between outcome reporting quality and other variables. RESULTS: Eighty publications reporting data from 10,924 participants were included. Seventeen different surgical interventions were evaluated. One hundred different outcomes and 112 outcome measures were reported. Outcomes were inconsistently reported across trials; for example, 43 trials reported anatomical treatment success rates (12 outcome measures), 25 trials reported quality of life (15 outcome measures) and eight trials reported postoperative pain (seven outcome measures). Multivariate linear regression demonstrated a relationship between outcome reporting quality with methodological quality (β = 0.412; P = 0.018). No relationship was demonstrated between outcome reporting quality with impact factor (β = 0.078; P = 0.306), year of publication (β = 0.149; P = 0.295), study size (β = 0.008; P = 0.961) and commercial funding (β = -0.013; P = 0.918). CONCLUSIONS: Anterior-compartment vaginal prolapse trials report many different outcomes and outcome measures and often neglect to report important safety outcomes. Developing, disseminating and implementing a core outcome set will help address these issues
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