12 research outputs found
Dendritic Cells Transfected with MHC Antigenic Determinants of CBA Mice Induce Antigen-Specific Tolerance in C57Bl/6 Mice
Background. Nonspecific immunosuppressive therapy for graft rejection and graft-versus-host disease (GVHD) is often accompanied by severe side effects such as opportunistic infections and cancers. Several approaches have been developed to suppress transplantation reactions using tolerogenic cells, including induction of FoxP3+ Tregs with antigen-loaded dendritic cells (DCs) and induction of CD4+IL-10+ cells with interleukin IL-10-producing DCs. Here, we assessed the effectiveness of both approaches in the suppression of graft rejection and GVHD. Methods. IL-10-producing DCs were generated by the transfection of DCs with DNA constructs encoding mouse IL-10. Antigen-loaded DCs from C57BL/6 mice were generated by transfection with DNA constructs encoding antigenic determinants from the H2 locus of CBA mice which differ from the homologous antigenic determinants of C57BL/6 mice. Results. We found that both IL-10-producing DCs and antigen-loaded immature DCs could suppress graft rejection and GVHD but through distinct nonspecific and antigen-specific mechanisms, respectively. Discussion. We provide data that the novel approach for DCs antigen loading using DNA constructs encoding distinct homologous determinants derived from major histocompatibility complex genes is effective in antigen-specific suppression of transplantation reactions. Such an approach eliminates the necessity of donor material use and may be useful in immunosuppressive therapy side effects prevention
Distribution of the geometric standard deviation (GSD) of errors associated with measurements of thyroid activity and of thyroid mass across individuals within the cohort.
Variation of excess relative risk with age at the time of the accident (using 1<sup>st</sup> regression calibration method, adapted from Kukush <i>et al.</i>[13]).
<p>Other details as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085723#pone-0085723-g004" target="_blank">Figure 4</a>.</p
Distribution of the geometric standard deviation (GSD) of errors associated with assessments of thyroid activity GSD as a function of TD-10 thyroid dose.
<p>Low dose range.</p
Analysis of curvature in fits of EOR model (2) with or without adjustment for dose errors using regression calibration, for TD-10 doses.
<p>All models have underlying rates adjusted for age (treated categorically) and gender. Unless otherwise stated all CI are profile-likelihood based.</p>a<p>unless otherwise stated all <i>p</i>-values refer to the improvement in fit of the current row in the Table with that of the model fitted in the row immediately above.</p>b<p><i>p</i>-value of improvement in fit compared with a model with no dose terms.</p
Dose response (+95 CI) for thyroid cancer in relation to TD-10 unadjusted dose, and regression-calibration-adjusted dose (using 1<sup>st</sup> method, adapted from Kukush <i>et al.</i>[13]).
<p>The models are adjusted for age (treated categorically) and gender in the baseline. Dashed red line shows odds ratio  = 1.</p
Results of fits of optimal excess relative risk model (2) (maximum likelihood fits and 95% profile CI), all based on TD-10 dose estimates adjusted using 1<sup>st</sup> regression calibration method (of Kukush <i>et al.</i>). All models have underlying rates adjusted for age (treated categorically) and gender. Parameters are given (with 95% CI), with associated <i>p</i>-values.<sup>a</sup> Unless otherwise stated all CI are profile-likelihood based.
a<p>Unless otherwise stated all <i>p</i>-values refer to improvement in fit of model immediately above indicated one in the Table.</p>b<p><i>p</i>-value for improvement in fit over null model (without linear dose term).</p>c<p><i>p</i>-value for improvement in fit over model 2, linear-exponential in dose.</p>d<p>indications of lack of convergence.</p>e<p>Wald-based CI.</p