Distinct dynamic behavioural response to social exclusion in male patients with a history of alcohol dependence.

Social exclusion contributes to alcohol consumption, whereas the development of alcohol dependence (AD) can in turn lead to the social exclusion of people with AD. Previous research observed altered neural responses to experimentally induced social exclusion (i.e., Cyberball game) in patients with AD. In addition, inflammation has been associated with both social behaviours and AD. Our study aimed to investigate the dynamic behavioural response and the inflammatory effects of social exclusion in male patients with a history of AD. To this end, we analysed dynamic changes in ball tossing during a partial exclusion Cyberball game and the cytokine interleukin (IL)-1b in saliva in 31 male patients who had a history of AD and 29 gender-matched healthy controls without AD. Participants were included in the first 2 min of the Cyberball game and then excluded by one of the two co-players in the proceeding 5 min. Saliva was collected three times: one before and two after the Cyberball game. Across groups, participants passed the ball more often to the excluder during the partial exclusion period. Analysis using piece-wise linear mixed models showed that patients rapidly increased ball tosses to the excluder upon exclusion, which lasted to the late response phase, whereas the early behavioural response to exclusion took longer for controls. There was no significant change of salivary IL-1b level to exclusion in either patients or controls. The results indicate a distinct dynamic behavioural response to social exclusion in male patients with a history of AD.

A revised strategy for monitoring BKV-specific cellular immunity in kidney transplant patients.

Reactivation of Polyomavirus BKV is a severe complication in kidney transplant patients. Current treatment requires close monitoring, and modification of immunosuppressive drugs. As an important additional tool, the monitoring of BKV immunity has been based on detection of cytokine-secreting T cells upon BKV-antigen challenge. However, low frequent BKV-specific T cells are often barely detectable and their roles in BKV clearance remain unclear. Here, we analyzed the effects of immunosuppressive agents on BKV-specific T cells in vitro. Significant reductions in expression of several markers, and reduced killing functions upon treatment with calcineurin but not mTOR inhibitors were detected. However, effects of these drugs on expression of surface markers and GranzymeB were substantially less striking than effects on cytokine expression. Consequently, we applied a novel detection strategy for BKV-specific T cells in immunosuppressed kidney transplant patients using these more robust markers, and showed significantly improved sensitivity compared with the conventional IFNγ-based method. Using this strategy and 17-color flow cytometry, we found BKV-specific helper and cytolytic CD4+ T-cell subsets that differed in their memory phenotype, which corresponded with BKV clearance in kidney transplant patients. Thus, our results offer an improved detection strategy for BKV-specific T cells in kidney transplant patients, and shed light on the contributions of these cells to BKV clearance.

Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus.

Background: Depression and anxiety are known to be associated with stress-induced changes in the immune system. Bothersome tinnitus can be related to stress and often co-occurs with depression and anxiety. This study investigates associations of psychological and audiological tinnitus-related factors with inflammatory parameters and immune cell subsets in chronic tinnitus patients as well as treatment-related effects. Methods: This longitudinal study of inpatients treated with compact multimodal tinnitus-specific cognitive behavioral therapy included four repeated measurement sessions: baseline (N = 41), treatment end, 7.8-week (N = 35), and 13.8-week follow-up (N = 34). Data collection included audiometric testing, blood sampling, and psychometric questionnaires: Tinnitus Handicap Inventory (THI), Perceived Stress Questionnaire (PSQ-20), and Hospital Anxiety Depression Scale (HADS). Flow cytometry was used to analyze immune cell subsets. Statistical analyses comprised correlation and network analysis (cross-sectional), and linear mixed effect models (longitudinal). Results: Bootstrapped network analysis showed negative averaged cross-sectional associations of cytotoxic natural killer (NKc) cell frequency (CD56 + CD16+) and PSQ-20 (-0.21 [-0.48, 0]) and of regulatory natural killer (NKreg) cell frequency (CD56 + CD16dim/-) and HADS anxiety (-0.14 [-0.38, 0]). No significant treatment effects were found. A negative predictive effect of baseline PSQ-20 scores (ß = -6.22 [-12.18, -0.26], p = 0.041) and a positive predictive effect of baseline ferritin levels (ß = 8.90 [2.76, 15.03], p = 0.004) on NKc cell frequency across the repeated measurement sessions were observed. Conclusion: We observed negative relationships between perceived stress levels and NKc cell frequency and between anxiety levels and NKreg cell frequency in chronic tinnitus patients. These exploratory results suggest stress-/anxiety-related immune alterations in bothersome tinnitus but need to be tested in further confirmatory studies with larger sample sizes. The potential of NK cells as biomarkers of emotional distress in chronic tinnitus should be further investigated.

Generation of a human induced pluripotent stem cell line from urinary cells of a healthy donor using integration free Sendai virus technology.

We have generated a human induced pluripotent stem cell (iPSC) line derived from urinary cells of a 28year old healthy female donor. The cells were reprogrammed using a non-integrating viral vector and have shown full differentiation potential. Together with the iPSC line, the donor provided blood cells for the study of immunological effects of the iPSC line and its derivatives in autologous and allogeneic settings. The line is available and registered in the human pluripotent stem cell registry as BCRTi005-A.

WITHDRAWN: Generation of a human induced pluripotent stem cell line from urinary cells of a healthy donor using integration free Sendai technology.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Stem Cell Res., 16 (2016) 133­136, http://dx.doi.org/10.1016/j.scr.2015.12.021. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Generation of a human induced pluripotent stem cell line from urinary cells of a healthy donor using an integration free vector.

We have generated a human induced pluripotent stem cell (iPSC) line derived from urinary cells of a 30 year old healthy female donor. The cells were reprogrammed using a non-integrating viral vector and have shown full differentiation potential. Together with the iPSC-line, the donor provided blood cells for the study of immunological effects of the iPSC line and its derivatives in autologous and allogeneic settings. The line is available and registered in the human pluripotent stem cell registry as BCRTi004-A.