Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Quantitative Detection of Schistosoma japonicum Cercariae in Water by Real-Time PCR

In China alone, an estimated 30 million people are at risk of schistosomiasis, caused by the Schistosoma japonicum parasite. Disease has re-emerged in several regions that had previously attained transmission control, reinforcing the need for active surveillance. The environmental stage of the parasite is known to exhibit high spatial and temporal variability, and current detection techniques rely on a sentinel mouse method which has serious limitations in obtaining data in both time and space. Here we describe a real-time PCR assay to quantitatively detect S. japonicum cercariae in laboratory samples and in natural water that has been spiked with known numbers of S. japonicum. Multiple primers were designed and assessed, and the best performing set, along with a TaqMan probe, was used to quantify S. japonicum. The resulting assay was selective, with no amplification detected for Schistosoma mansoni, Schistosoma haematobium, avian schistosomes nor organisms present in non-endemic surface water samples. Repeated samples containing various concentrations of S. japonicum cercariae showed that the real-time PCR method had a strong linear correlation (R2 = 0.921) with light microscopy counts, and the detection limit was below the DNA equivalent of half of one cercaria. Various cercarial concentrations spiked in 1 liter of natural water followed by a filtration process produced positive detection from 93% of samples analyzed. The real-time PCR method performed well quantifying the relative concentrations of various spiked samples, although the absolute concentration estimates exhibited high variance across replicated samples. Overall, the method has the potential to be applied to environmental water samples to produce a rapid, reliable assay for cercarial location in endemic areas

The role of schools in the spread of mumps among unvaccinated children: a retrospective cohort study

Contains fulltext : 98461.pdf (publisher's version ) (Open Access)BACKGROUND: In the Netherlands, epidemics of vaccine preventable diseases are largely confined to an orthodox protestant minority with religious objections to vaccination. The clustering of unvaccinated children in orthodox protestant schools can foster the spread of epidemics. School closure has nevertheless not been practiced up until now. A mumps epidemic in 2007-2008 gave us an opportunity to study the role of schools in the spread of a vaccine preventable disease in a village with low vaccination coverage. METHODS: A retrospective cohort study was conducted among the students in four elementary schools and their siblings. The following information was collected for each child: having had the mumps or not and when, school, age, MMR vaccination status, household size, presence of high school students in the household, religious denomination, and home village. The spread of mumps among unvaccinated children was compared for the four schools in a Kaplan-Meier analysis using a log-rank test. Cox proportional hazard analyses were performed to test for the influence of other factors. To correct for confounding, a univariate Cox regression model with only school included as a determinant was compared to a multivariate regression model containing all possible confounders. RESULTS: Out of 650 households with children at the schools, 54% completed a questionnaire, which provided information on 1191 children. For the unvaccinated children (N = 769), the Kaplan-Meier curves showed significant differences among the schools in their cumulative attack rates. After correction for confounding, the Cox regression analysis showed the hazard of mumps to be higher in one orthodox protestant school compared to the other (hazard ratio 1.43, p < 0.001). Household size independently influenced the hazard of mumps (hazard ratio 1.44, p < 0.005) with children in larger households running a greater risk. CONCLUSION: If and when unvaccinated children got mumps was determined by the particular school the children and their siblings attended, and by the household size. This finding suggests that school closure can influence the spread of an epidemic among orthodox protestant populations, provided that social distancing is adhered to as well. Further research on the effects of school closure on the final attack rate is nevertheless recommended

Clonal evolution of CD8+ T cell responses against latent viruses: relationship among phenotype, localization, and function

Human cytomegalovirus (hCMV) infection is characterized by a vast expansion of resting effector-type virus-specific T cells in the circulation. In mice, interleukin-7 receptor α (IL-7Rα)-expressing cells contain the precursors for long-lived antigen-experienced CD8(+) T cells, but it is unclear if similar mechanisms operate to maintain these pools in humans. Here, we studied whether IL-7Rα-expressing cells obtained from peripheral blood (PB) or lymph nodes (LNs) sustain the circulating effector-type hCMV-specific pool. Using flow cytometry and functional assays, we found that the IL-7Rα(+) hCMV-specific T cell population comprises cells that have a memory phenotype and lack effector features. We used next-generation sequencing of the T cell receptor to compare the clonal repertoires of IL-7Rα(+) and IL-7Rα(-) subsets. We observed limited overlap of clones between these subsets during acute infection and after 1 year. When we compared the hCMV-specific repertoire between PB and paired LNs, we found many identical clones but also clones that were exclusively found in either compartment. New clones that were found in PB during antigenic recall were only rarely identical to the unique LN clones. Thus, although PB IL-7Rα-expressing and LN hCMV-specific CD8(+) T cells show typical traits of memory-type cells, these populations do not seem to contain the precursors for the novel hCMV-specific CD8(+) T cell pool during latency or upon antigen recall. IL-7Rα(+) PB and LN hCMV-specific memory cells form separate virus-specific compartments, and precursors for these novel PB hCMV-specific CD8(+) effector-type T cells are possibly located in other secondary lymphoid tissues or are being recruited from the naive CD8(+) T cell pool. IMPORTANCE: Insight into the self-renewal properties of long-lived memory CD8(+) T cells and their location is crucial for the development of both passive and active vaccination strategies. Human CMV infection is characterized by a vast expansion of resting effector-type cells. It is, however, not known how this population is maintained. We here investigated two possible compartments for effector-type cell precursors: circulating acute-phase IL-7Rα-expressing hCMV-specific CD8(+) T cells and lymph node (LN)-residing hCMV-specific (central) memory cells. We show that new clones that appear after primary hCMV infection or during hCMV reactivation seldom originate from either compartment. Thus, although identical clones may be maintained by either memory population, the precursors of the novel clones are probably located in other (secondary) lymphoid tissues or are recruited from the naive CD8(+) T cell pool

The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data we further aimed to investigate the role of CD97 small isoform in gastric cancer progression in vivo by employing the cells with a stable CD97 small isoform knock-down and an orthotopic gastric cancer mouse model. We could demonstrate that the knock down of CD97/EGF1,2,5, led to a significant decrease in the number of cells penetrating the gelatin coated membrane as compared with control cells. In the gastric cancer mouse model, both the hypodermic and the orthotopic yielded tumor masses of the CD97/EGF1,2,5kd group and were significantly smaller than the control. Metastatic tumor cell number in early metastatic regional lymph nodes on post-operative day 42 was distinctly decreased in the CD97/EGF1,2,5kd group as compared with the SGC-NS group, and was accompanied with the downregulation of CD44, VEGFR, CD31 and CD97. We concluded in this study that CD97 small isoform not only supported gastric cancer local growth, but also promoted metastatic spread in orthotopically implanted mouse model suggesting involvement of the CD97 small isoform in the preparation of (pre)metastatic niche

Mechanistic framework to link root growth models with weather and soil physical properties, including example applications to soybean growth in Brazil

Background and aimsRoot elongation is generally limited by a combination of mechanical impedance and water stress in most arable soils. However, dynamic changes of soil penetration resistance with soil water content are rarely included in models for predicting root growth. Better modelling frameworks are needed to understand root growth interactions between plant genotype, soil management, and climate. Aim of paper is to describe a new model of root elongation in relation to soil physical characteristics like penetration resistance, matric potential, and hypoxia.MethodsA new diagrammatic framework is proposed to illustrate the interaction between root elongation, soil management, and climatic conditions. The new model was written in Matlab®, using the root architecture model RootBox and a model that solves the 1D Richards equations for water flux in soil. Inputs: root architectural parameters for Soybean; soil hydraulic properties; root water uptake function in relation to matric flux potential; root elongation rate as a function of soil physical characteristics. Simulation scenarios: (a) compact soil layer at 16 to 20 cm; (b) test against a field experiment in Brazil during contrasting drought and normal rainfall seasons.Results(a) Soil compaction substantially slowed root growth into and below the compact layer. (b) Simulated root length density was very similar to field measurements, which was influenced greatly by drought. The main factor slowing root elongation in the simulations was evaluated using a stress reduction function.ConclusionThe proposed framework offers a way to explore the interaction between soil physical properties, weather and root growth. It may be applied to most root elongation models, and offers the potential to evaluate likely factors limiting root growth in different soils and tillage regimes

Hepatitis B screening in the Turkish-Dutch population in Rotterdam, the Netherlands; qualitative assessment of socio-cultural determinants

Background. Hepatitis B is an important health problem in the Turkish community in the Netherlands. Increased voluntary screening is necessary in this community, to detect individuals eligible for treatment and to prevent further transmission of the disease. Methods. We investigated socio-cultural determinants associated with hepatitis B screening in male and female, first and second generation Turkish migrants, by means of Focus Group Discussions. Results. Socio-cultural themes related to hepatitis B screening were identified; these were social norm, social support, sensitivity regarding sexuality, reputation, responsiveness to authority, religious responsibility, cleanliness and religious doctrine regarding health and disease, and the perceived efficacy of Dutch health care services. Motivating factors were the (religious) responsibility for one's health, the perceived obligation when being invited for screening, and social support to get tested for hepatitis B. Perceived barriers were the association of hepatitis B screening with STDs or sexual activity, the perception of low control over one's health, and the perceived low efficacy of the Dutch health care services. Reputation could act as either a motivator or barrier. Conclusion. This study identified relevant socio-cultural themes related to hepatitis B screening, which may serve to customize interventions aimed at the promotion of voluntary hepatitis B screening in the Turkish-Dutch population in the Netherlands