Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin

Cerebrospinal fluid (CSF) from healthy individuals contains between 1,000 and 3,000 leukocytes per ml. Little is known about trafficking patterns of leukocytes between the systemic circulation and the noninflamed CNS. In the current study, we characterized the surface phenotype of CSF cells and defined the expression of selected adhesion molecules on vasculature in the choroid plexus, the subarachnoid space surrounding the cerebral cortex, and the cerebral parenchyma. Using multicolor flow cytometry, we found that CSF cells predominantly consisted of CD4+/CD45RA-/CD27+/CD69+-activated central memory T cells expressing high levels of CCR7 and L-selectin. CD3+ T cells were present in the choroid plexus stroma in autopsy CNS tissue sections from individuals who died without known neurological disorders. P- and E-selectin immunoreactivity was detected in large venules in the choroid plexus and subarachnoid space, but not in parenchymal microvessels. CD4+ T cells in the CSF expressed high levels of P-selectin glycoprotein ligand 1, and a subpopulation of circulating CD4+ T cells displayed P-selectin binding activity. Intercellular adhesion molecule 1, but not vascular cell adhesion molecule 1 or mucosal addressin cell adhesion molecule 1, was expressed in choroid plexus and subarachnoid space vessels. Based on these findings, we propose that T cells are recruited to the CSF through interactions between P-selectin/P-selectin ligands and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 in choroid plexus and subarachnoid space venules. These results support the overall hypothesis that activated memory T cells enter CSF directly from the systemic circulation and monitor the subarachnoid space, retaining the capacity to either initiate local immune reactions or return to secondary lymphoid organs.     

Protective effects of a DNA vaccine expressing the infectious salmon anemia virus hemagglutinin-esterase in Atlantic salmon

Infectious salmon anemia (ISA) is a disease, caused by an orthomyxovirus, which has considerable economic impact on farming of Atlantic salmon. Here we describe the results of immunization against ISA using plasmids expressing the ISA virus hemagglutinin-esterase (HE). Immunized Atlantic salmon demonstrated moderate protection after challenge with ISA virus, with relative percent survival of 39.5 and 60.5 in two parallel groups. No protection was seen after immunization using a plasmid expressing the ISA virus nucleoprotein. Fish in the HE-immunized group had earlier onset of clearance of the virus than control fish. There was no detectable ISA virus specific humoral response after immunization. After challenge a specific humoral response could be demonstrated in the fish in all groups, but no correlation between this response and protection was found.     

Bodily pain and associated mental distress among immigrant adolescents

Abstract Objective The aim of this study was to describe differences among immigrant groups in bodily pain, and analyze its association with mental distress. Method A population-based cross-sectional study was carried out involving tenth grade pupils in Oslo. Of the 7,343 pupils that participated, one-quarter were first- or second-generation immigrants. The Hopkins Symptom Checklist-10 was used to measure mental distress. All information on pain and mental distress was self-reported. Results Girls reported more bodily pain from all types of pain. Headache was the most prevalent pain site across gender and immigrant groups. Strong associations between mental distress and number of pain sites were found for all immigrant groups. Neck and shoulder pain yielded the highest odds ratio (OR) for mental distress among the majority of the immigrant groups. The Sub-Saharan African group had the highest adjusted OR for mental distress [OR=9.8 (1.1–82.7)] when reporting three or more pain sites, and the Indian Subcontinent the lowest [OR=4.0 (1.8–8.8)]. Conclusion The differences in number and types of pain were small, though significant between the different immigrant groups. Adolescents from Sub-Saharan Africa seem to react with more mental distress to bodily pain than adolescents emigrating from the Indian Subcontinent.     

Behavioral effects of intra-cranial self-stimulation in an animal model of attention-deficit/hyperactivity disorder (ADHD)

Attention deficit/hyperactivity disorder (ADHD), characterized by inappropriate levels of activity, attention, and impulsivity, has been suggested to be caused by changes in reinforcement and extinction processes possibly linked to dysfunctioning dopamine systems. The present study investigated reinforcement processes in spontaneously hypertensive rats (SHR), an animal model of ADHD. Using intra-cranial self-stimulation (ICSS), behavioral effects of varying current intensity, reinforcer density, and reinforcer delay were tested. Current was varied in order to find the weakest current producing the maximal response rate (optimal current) in the SHR and the controls during high (120 reinforcers/min) and low reinforcer densities (1 reinforcer/min). The results showed that optimal current was significantly lower in the SHR than in the controls during high reinforcer density while maximal response rates were not significantly different. During low reinforcer density, optimal current was not significantly different in the two strains, but maximal response rate was significantly higher in the SHR than in the controls. The SHR produced more responses during the testing of reinforcer density, but changes in reinforcer density affected response rates similarly in the two strains. The decrease in response rate as a function of reinforcer delay was more pronounced in the SHR than in the controls. Overall, more responses with short inter-response times (IRT) were found in the SHR compared to the controls during intermittent reinforcement. The results are consistent with a steepened delay-of-reinforcement gradient in SHR.     

Effects of delayed reinforcers on the behavior of an animal model of attention-deficit/hyperactivity disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD), affecting 3-5% of grade-school children, is a behavioral disorder characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity. It has been suggested that the symptoms are caused by altered reinforcement and extinction processes, behaviorally described as an abnormally short and steep delay-of-reinforcement gradient in ADHD. The present study tested predictions from the suggested shortened and steepened delay gradient in ADHD in an animal model, the spontaneously hypertensive rats (SHRs). It was predicted that SHR responding during baseline would mainly consist of responses with short inter-response times, and that responding would be more rapidly reduced in the SHR than in the controls by the introduction of a time interval between the response and reinforcer delivery. Effects of a resetting delay of reinforcement procedure with water as the reinforcer were tested on two baseline reinforcement schedules: variable interval 30 s (VI 30 s) and conjoint variable interval 60 s differential reinforcement of high rate 1s (VI 60 s DRH 1 s). The results showed a higher rate of responses in the SHR than in the controls during baseline, mainly consisting of responses with short inter-response times. The statistical analyses showed that response rates decreased more rapidly as a function of reinforcer delay in the SHR than in the controls. The analyses of the estimates of the reinforcer decay parameter showed no strain differences during the VI 30 s schedule but showed a significant strain difference at the end, but not at the start, of the sessions during the VI 60 s DRH 1 s schedule. In general, the results support predictions from the suggested steepened delay gradient in SHR. However, the predictions were only partly confirmed by the analyses of the decay parameter.     

Adolescents with a childhood experience of parental divorce: a longitudinal study of mental health and adjustment

**This is a prospective Norwegian study of a group of adolescents with an experience of parental divorce or separation (n=413) and a comparison group without this experience (n=1758). Mean age at T1 was 14.4 years and mean age at T2 was 18.4 years. Parental divorce was prospectively associated with a relative change in anxiety and depression, subjective well-being, self-esteem, and school problems. Considering boys separately, parental divorce was prospectively associated only with school problems. Among the girls, divorce was prospectively associated with all variables. The effect of divorce on relative change was partially mediated by paternal absence.     

Plasmacytoid dendritic cells activate allergen-specific TH2 memory cells: modulation by CpG oligodeoxynucleotides

BACKGROUND: Plasmacytoid dendritic cells (PDCs) accumulate in the nasal mucosa of allergic rhinitis patients, but their function in upper airway allergy has not been determined. CpG oligodeoxynucleotides, potent adjuvants in immunotherapeutic strategies in animal models, are especially effective at activating PDCs. These cells are therefore potential targets for immunomodulation in humans. OBJECTIVE: In this study, PDCs were compared with CD11c+ dendritic cells (DCs), a very potent antigen-presenting cell type, for their capacity to induce allergen-dependent activation of TH2 memory cells. Then, we investigated whether CpG-activated PDCs were able to modulate the allergen-specific TH2 memory response. METHODS: DCs were isolated from patients with upper airway allergy and cocultured with autologous CD4+ T cells with or without grass pollen extract and CpG. In some experiments cells were restimulated with allergen-pulsed monocyte-derived DCs. T-cell activation was measured by their proliferative response and cytokine production. RESULTS: PDCs stimulated allergen-dependent T-cell proliferation and TH2 cytokine production as efficiently as CD11c+ DCs. CpG-activated PDCs inhibited allergen-dependent proliferation of TH2 memory cells and markedly increased IFN-gamma production in PDC/T-cell cocultures; the former effect depended on the CpG-induced IFN-alpha/beta production by the PDCs. CONCLUSION: Our results demonstrated that PDCs efficiently drive allergen-dependent TH2 memory responses, suggesting that they play an active role in the allergic reaction. However, in the presence of CpG, PDCs were responsible for increased production of the TH1-related cytokines IFN-alpha and IFN-gamma, indicating that mucosal PDCs may be targets for CpG-based immunotherapeutic strategies against airway allergy.