83 research outputs found
from a better etiological understanding, through valid diagnosis, to more effective health care
Background Autism Spectrum Disorder (ASD) is a severe, lifelong
neurodevelopmental disorder with early onset that places a heavy burden on
affected individuals and their families. Due to the need for highly
specialized health, educational and vocational services, ASD is a cost-
intensive disorder, and strain on health care systems increases with
increasing age of the affected individual. Methods The ASD-Net will study
Germany’s largest cohort of patients with ASD over the lifespan. By combining
methodological expertise from all levels of clinical research, the ASD-Net
will follow a translational approach necessary to identify neurobiological
pathways of different phenotypes and their appropriate identification and
treatment. The work of the ASD-Net will be organized into three clusters
concentrating on diagnostics, therapy and health economics. In the diagnostic
cluster, data from a large, well-characterized sample (N = 2568) will be
analyzed to improve the efficiency of diagnostic procedures. Pattern
classification methods (machine learning) will be used to identify algorithms
for screening purposes. In a second step, the developed algorithm will be
tested in an independent sample. In the therapy cluster, we will unravel how
an ASD-specific social skills training with concomitant oxytocin
administration can modulate behavior through neurobiological pathways. For the
first time, we will characterize long-term effects of a social skills training
combined with oxytocin treatment on behavioral and neurobiological phenotypes.
Also acute effects of oxytocin will be investigated to delineate general and
specific effects of additional oxytocin treatment in order to develop
biologically plausible models for symptoms and successful therapeutic
interventions in ASD. Finally, in the health economics cluster, we will assess
service utilization and ASD-related costs in order to identify potential needs
and cost savings specifically tailored to Germany. The ASD-Net has been
established as part of the German Research Network for Mental Disorders,
funded by the BMBF (German Federal Ministry of Education and Research).
Discussion The highly integrated structure of the ASD-Net guarantees sustained
collaboration of clinicians and researchers to alleviate individual distress,
harm, and social disability of patients with ASD and reduce costs to the
German health care system. Trial registration Both clinical trials of the ASD-
Net are registered in the German Clinical Trials Register: DRKS00008952
(registered on August 4, 2015) and DRKS00010053 (registered on April 8, 2016)
EOMES and IL-10 regulate antitumor activity of T regulatory type 1 CD4 + T cells in chronic lymphocytic leukemia
The transcription factor eomesodermin (EOMES) promotes interleukin (IL)-10 expression in CD4(+) T cells, which has been linked to immunosuppressive and cytotoxic activities. We detected cytotoxic, programmed cell death protein-1 (PD-1) and EOMES co-expressing CD4(+) T cells in lymph nodes (LNs) of patients with chronic lymphocytic leukemia (CLL) or diffuse large B-cell lymphoma. Transcriptome and flow cytometry analyses revealed that EOMES does not only drive IL-10 expression, but rather controls a unique transcriptional signature in CD4(+) T cells, that is enriched in genes typical for T regulatory type 1 (T(R)1) cells. The T(R)1 cell identity of these CD4(+) T cells was supported by their expression of interferon gamma and IL-10, as well as inhibitory receptors including PD-1. T(R)1 cells with cytotoxic capacity accumulate also in Eµ-TCL1 mice that develop CLL-like disease. Whereas wild-type CD4(+) T cells control TCL1 leukemia development after adoptive transfer in leukopenic Rag2(−/)(−) mice, EOMES-deficient CD4(+) T cells failed to do so. We further show that T(R)1 cell-mediated control of TCL1 leukemia requires IL-10 receptor (IL-10R) signaling, as Il10rb-deficient CD4(+) T cells showed impaired antileukemia activity. Altogether, our data demonstrate that EOMES is indispensable for the development of IL-10-expressing, cytotoxic T(R)1 cells, which accumulate in LNs of CLL patients and control TCL1 leukemia in mice in an IL-10R-dependent manner
- …