IL-15 augments TCR-induced CD4⁺ T cell expansion in vitro by inhibiting the suppressive function of CD25High CD4⁺ T cells

Due to its critical role in NK cell differentiation and CD8(+) T cell homeostasis, the importance of IL-15 is more firmly established for cytolytic effectors of the immune system than for CD4(+) T cells. The increased levels of IL-15 found in several CD4(+) T cell-driven (auto-) immune diseases prompted us to examine how IL-15 influences murine CD4(+) T cell responses to low dose TCR-stimulation in vitro. We show that IL-15 exerts growth factor activity on both CD4(+) and CD8+ T cells in a TCR-dependent and Cyclosporin A-sensitive manner. In CD4(+) T cells, IL-15 augmented initial IL-2-dependent expansion and once IL-15R alpha was upregulated, IL-15 sustained the TCR-induced expression of IL-2/15R beta, supporting proliferation independently of secreted IL-2. Moreover, IL-15 counteracts CD4(+) T cell suppression by a gradually expanding CD25(High)CD4(+) T cell subset that expresses Foxp3 and originates from CD4(+)CD25(+) Tregs. These in vitro data suggest that IL-15 may dramatically strengthen the T cell response to suboptimal TCR-triggering by overcoming an activation threshold set by Treg that might create a risk for autoimmune pathology

Visualization of the medial forebrain bundle using diffusion tensor imaging

Diffusion tensor imaging is a technique that enables physicians the portrayal of white matter tracts in vivo. We used this technique in order to depict the medial forebrain bundle (MFB) in 15 consecutive patients between 2012 and 2015. Men and women of all ages were included. There were six women and nine men. The mean age was 58.6 years (39–77). Nine patients were candidates for an eventual deep brain stimulation. Eight of them suffered from Parkinson‘s disease and one had multiple sclerosis. The remaining six patients suffered from different lesions which were situated in the frontal lobe. These were 2 metastasis, 2 meningiomas, 1 cerebral bleeding, and 1 glioblastoma. We used a 3DT1-sequence for the navigation. Furthermore T2- and DTI- sequences were performed. The FOV was 200 × 200 mm2, slice thickness 2 mm, and an acquisition matrix of 96 × 96 yielding nearly isotropic voxels of 2 × 2 × 2 mm. 3-Tesla-MRI was carried out strictly axial using 32 gradient directions and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2. b-value was 800 s/mm2. The maximal angle was 50°. Additional scanning time was < 9 min. We were able to visualize the MFB in 12 of our patients bilaterally and in the remaining three patients we depicted the MFB on one side. It was the contralateral side of the lesion. These were 2 meningiomas and one metastasis. Portrayal of the MFB is possible for everyday routine for neurosurgical interventions. As part of the reward circuitry it might be of substantial importance for neurosurgeons during deep brain stimulation in patients with psychiatric disorders. Surgery in this part of the brain should always take the preservation of this white matter tract into account

Holmes tremor in a patient with progressive multifocal leukoencephalopathy.

BACKGROUND: Progressive multifocal leukencephalopathy (PML) is a rare, sometimes fatal viral disease in patients with primary or secondary immunosuppression. CASE DESCRIPTION: A 57-year-old immunocompetent female with intractable Holmes tremor and elongated unique brainstem lesion reported to our hospital. The cerebrospinal fluid (CSF) screening for John Cunningham virus was negative and the diagnosis was established by brain biopsy. The course was rapidly fatal. CONCLUSION: This atypical presentation of PML in an immunocompetent patient illustrates that diagnosis can be missed without brain biopsy

IL-15 augments TCR-Induced CD4+ T Cell Expansion In Vitro by Inhibiting the Suppressive Function of CD25High CD4+ T Cells

Due to its critical role in NK cell differentiation and CD8+ T cell homeostasis, the importance of IL-15 is more firmly established for cytolytic effectors of the immune system than for CD4+ T cells. The increased levels of IL-15 found in several CD4+ T cell-driven (auto-) immune diseases prompted us to examine how IL-15 influences murine CD4+ T cell responses to low dose TCR-stimulation in vitro. We show that IL-15 exerts growth factor activity on both CD4+ and CD8+ T cells in a TCR-dependent and Cyclosporin A-sensitive manner. In CD4+ T cells, IL-15 augmented initial IL-2-dependent expansion and once IL-15Rα was upregulated, IL-15 sustained the TCR-induced expression of IL-2/15Rβ, supporting proliferation independently of secreted IL-2. Moreover, IL-15 counteracts CD4+ T cell suppression by a gradually expanding CD25HighCD4+ T cell subset that expresses Foxp3 and originates from CD4+CD25+ Tregs. These in vitro data suggest that IL-15 may dramatically strengthen the T cell response to suboptimal TCR-triggering by overcoming an activation threshold set by Treg that might create a risk for autoimmune pathology

ATOPIE ET ALLERGIE DE CONTACT

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Diffusion tensor imaging--arcuate fasciculus and the importance for the neurosurgeon.

OBJECTIVE: Tumors in eloquent areas of the brain like Broca or Wernicke might have disastrous consequences for patients. We intended to visualize the arcuate fasciculus (AF) and to demonstrate his relation with the corticospinal tract and the visual pathway using diffusion tensor imaging (DTI). METHODS: We depicted between 2012 and 2014 the AF in 71 patients. Men and women of all ages were included. Eleven patients had postoperative controls also. We used a 3DT1-sequence for the navigation. Furthermore T2- and DTI-sequences were performed. The FOV was 200 x 200 mm(2), slice thickness 2mm, and an acquisition matrix of 96 x 96 yielding nearly isotropic voxels of 2 x 2 x 2 mm. 3-Tesla-MRI was carried out strictly axial using 32 gradient directions and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2. b-Value was 800 s/mm(2). Additional scanning time was less than 9 min. RESULTS: AF was portrayed in 63 patients bilaterally. In one glioblastoma patient it was impossible to visualize the left AF and in seven other patients we could not portray the right one. The lesions affected AF by disrupting or displacing the fibers. CONCLUSIONS: DTI might be a useful tool to portray AF. It is time-saving and can be used to preserve morbidity in patients with lesions in eloquent brain areas. It might give deeper insights of the white matter and the reorganization of AF-fibers postoperatively

Susceptibility-Weighted MRI for Deep Brain Stimulation: Potentials in Trajectory Planning

Background: Deep brain stimulation (DBS) trajectory plan- ning is mostly based on standard 3-D T1-weighted gado- linium-enhanced MRI sequences (T1-Gd). Susceptibility- weighted MRI sequences (SWI) show neurovascular struc- tures without the use of contrast agents. The aim of this study was to investigate whether SWI might be useful in DBS trajectory planning. Methods: We performed bilateral DBS planning using conventional T1-Gd images of 10 patients with different kinds of movement disorders. Afterwards, we matched SWI sequences and compared the visibility of vas- cular structures in both imaging modalities. Results: By ana- lyzing 100 possible trajectories, we found a potential vascu- lar conflict in 13 trajectories based on T1-Gd in contrast to 53 in SWI. Remarkably, all vessels visible in T1-Gd were also de- picted in SWI, whereas SWI showed many additional vascular structures which could not be identified in T1-Gd. Conclu- sion/Discussion: The sensitivity for detecting neurovascular structures for DBS planning seems to be significantly higher in SWI. As SWI does not require a contrast agent, we suggest that SWI may be a valuable alternative to T1-Gd MRI for DBS trajectory planning. Furthermore, the data analysis suggests that vascular interactions of DBS trajectories might be more frequent than expected from the very low incidence of symptomatic bleedings. The explanation for this is currently the subject of debate and merits further studies