Pregnancy Enables Expansion of Disease-Specific Regulatory T Cells in an Animal Model of Multiple Sclerosis.

Disease activity of autoimmune disorders such as multiple sclerosis and its mouse model experimental autoimmune encephalomyelitis (EAE) is temporarily suppressed by pregnancy. However, whether disease amelioration is due to nonspecific immunomodulation or mediated by Ag-specific regulation of disease-causing conventional T cells (Tcon) and immunosuppressive regulatory T cells (Tregs) remains elusive. In the current study, we systematically analyzed changes of the TCRß repertoire driven by EAE and pregnancy using TCR sequencing. We demonstrate that EAE, but not pregnancy, robustly increased TCR repertoire clonality in both peripheral Tcon and Treg. Notably, pregnancy was required for the expansion of Treg harboring the dominant EAE-associated TRBV13-2 chain and increased the frequency of EAE-associated clonotypes within the Treg compartment. Our findings indicate that pregnancy supports the expansion of Treg clonotypes that are equipped to recognize EAE-associated Ags. These Treg are thereby particularly suited to control corresponding encephalitogenic Tcon responses and likely contribute to pregnancy-associated protection in autoimmunity.

Production of IL-17 by MAIT Cells Is Increased in Multiple Sclerosis and Is Associated with IL-7 Receptor Expression.

Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism. In this study, we characterized MAIT cells from the peripheral blood of MS patients in comparison with healthy individuals with respect to their type-17 differentiation. We found a specific increase of IL-17+ MAIT cells as well as an increased expression of retinoic acid-related orphan receptor (ROR)γt and CCR6 in MAIT cells from MS patients, whereas the expression of T cell activation markers HLA-DR and CD38 was not different. IL-17 production by MAIT cells furthermore correlated with the surface expression level of the IL-7 receptor α-chain (CD127), which was significantly increased on MAIT cells from MS patients in comparison with healthy individuals. In summary, our findings indicate an augmented type-17 differentiation of MAIT cells in MS patients associated with their IL-7 receptor surface expression, implicating a proinflammatory role of these unconventional T cells in MS immunopathology.

Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function.

Recent association studies have linked numerous genetic variants with an increased risk for multiple sclerosis, although their functional relevance remains largely unknown. Here we investigated phenotypical and functional consequences of a genetic variant in the CD226 gene that, among other autoimmune diseases, predisposes to multiple sclerosis. Phenotypically, effector and regulatory CD4(+) memory T cells of healthy individuals carrying the predisposing CD226 genetic variant showed, in comparison to carriers of the protective variant, reduced surface expression of CD226 and an impaired induction of CD226 after stimulation. This haplotype-dependent reduction in CD226 expression on memory T cells was abrogated in patients with multiple sclerosis, as CD226 expression was comparable to healthy risk haplotype carriers irrespective of genetic variant. Functionally, FOXP3-positive regulatory T cells from healthy carriers of the genetic protective variant showed superior suppressive capacity, which was again abrogated in multiple sclerosis patients. Mimicking the phenotype of human CD226 genetic risk variant carriers, regulatory T cells derived from Cd226-deficient mice showed similarly reduced inhibitory activity, eventually resulting in an exacerbated disease course of experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. Therefore, by combining human and mouse analyses we show that CD226 exhibits an important role in the activation of regulatory T cells, with its genetically imposed dysregulation impairing regulatory T cell function.

[Resource-oriented assessment using the German Competence Analysis Questionnaire (Kompetenzanalyseverfahren, KANN) - verification of the KANN's validity as measured by the Child Behavior Checklist (CBCL/4-18) in the context of child and youth welfare]. / Ressourcenorientierte Diagnostik mit Hilfe des Kompetenz- analyseverfahrens (KANN). Überprüfung der Aussagekraft des KANN gemessen anhand der Child Behavior Checklist (CBCL/4-18) im Kontext der Kinder- und Jugendhilfe.

OBJECTIVE: The German Competence Analysis Questionnaire (Kompetenzanalyseverfahren, KANN) is an external assessment tool used to determine observable personal resources (= competences) in children and adolescents. The present paper examines the validity of the KANN based on additionally collected data of behavior disorders as measured by the Child Behavior Checklist (CBCL/4-18). The main objective is to explore whether the KANN scales are able to differentiate between children and adolescents with or without internalizing and/or externalizing behavior disorders. METHOD: The sample consists of n = 450 young people (aged 6 to 22 years) under the care of child and youth welfare services assessed between 2010 and 2012 by their group careworkers using KANN and CBCL as part of the ongoing quality development system "moses." RESULTS: According to the discriminant analysis the KANN scale "Empathy & Fairness" differentiates very well between youths with or without behavior disorders, particularly those with externalizing problems. The KANN scale "Leisure Behavior & Peer Groups" contributes the highest rate of differentiation of internalizing problems. The hit ratios of the discriminant analyses reach values of up to 76.2 %. CONCLUSIONS: The ability of the KANN scales to differentiate behavior disorders underlines the validity of the KANN.

Comparison of optical coherence tomography angiography and narrow-band imaging using a bimodal endoscope.

We present coregistered images of tissue vasculature that allow a direct comparison between the performance of narrow-band imaging (NBI) and optical coherence tomography angiography (OCTA). Images were generated with a bimodal endomicroscope having a size of 15 × 2.4 × 3.3 3 ( l , w , h ) that combines two imaging channels. The white light imaging channel was used to perform NBI, the current gold standard for endoscopic visualization of vessels. The second channel allowed the simultaneous acquisition of optical coherence tomography (OCT) and OCTA images, enabling a three-dimensional (3-D) visualization of morphological as well as functional tissue information. In order to obtain 3-D OCT images scanning of the light-transmitting fiber was implemented by a small piezoelectric tube. A field of view of ∼1.1 mm was achieved for both modalities. Under the assumption that OCTA can address current limitations of NBI, their performance was studied and compared during in vivo experiments. The preliminary results show the potential of OCT regarding an improved visualization and localization of vessel beds, which can be beneficial for diagnosis of pathological conditions.

Stereolithographic 3D Printing with Renewable Acrylates.

The accessibility of cost-competitive renewable materials and their application in additive manufacturing is essential for an efficient biobased economy. We demonstrate the rapid prototyping of sustainable resins using a stereolithographic 3D printer. Resin formulation takes place by straightforward mixing of biobased acrylate monomers and oligomers with a photoinitiatior and optical absorber. Resin viscosity is controlled by the monomer to oligomer ratio and is determined as a function of shear rate by a rheometer with parallel plate geometry. A stereolithographic apparatus charged with the biobased resins is employed to produce complex shaped prototypes with high accuracy. The products require a post-treatment, including alcohol rinsing and UV irradiation, to ensure complete curing. The high feature resolution and excellent surface finishing of the prototypes is revealed by scanning electron microscopy.

Biobased Acrylate Photocurable Resin Formulation for Stereolithography 3D Printing.

To facilitate the ongoing transition toward a circular economy, the availability of renewable materials for additive manufacturing becomes increasingly important. Here, we report the successful fabrication of complex shaped prototypes from biobased acrylate photopolymer resins, employing a commercial stereolithography apparatus (SLA) 3D printer. Four distinct resins with a biobased content ranging from 34 to 67% have been developed. All formulations demonstrated adequate viscosity and were readily polymerizable by the UV-laser-based SLA process. Increasing the double-bond concentration within the resin results in stiff and thermally resilient 3D printed products. High-viscosity resins lead to high-resolution prototypes with a complex microarchitecture and excellent surface finishing, comparable to commercial nonrenewable resins. These advances can facilitate the wide application of biobased resins for construction of new sustainable products via stereolithographic 3D printing methods.