HHV-6 Specific T-Cell Immunity in Healthy Children and Adolescents

Objective: Primary infection with human herpes virus 6 (mainly HHV-6B) commonly occurs in the first 2 years of life leading to persistence and the possibility of virus reactivation later in life. Consequently, a specific cellular immune response is essential for effective control of virus reactivation. We have studied cell-mediated immune response to HHV-6 (U54) in healthy children and adolescents.Materials and Methods: By flow cytometry, the amount of cytokine (interferon gamma—IFN- γ, interleukin 2—IL-2, tumor necrosis factor alpha—TNF-α) secreting T-cells were measured after 10 days of pre-sensitization and 6 h of re-stimulation with mixtures of pooled overlapping peptides from U54, staphylococcal enterotoxin B (SEB, positive control), or Actin (negative control) in healthy children and adolescents without any underlying immune disorder or infectious disease.Results: All individuals showed a virus-specific response for at least one cytokine in either CD4+ or CD8+ cells. Percentages of individuals with HHV-6-specific TNF-α response in CD4+ (48% of individuals) as well as CD8+ (56% of individuals) were always the highest. Our data show significantly higher frequencies of HHV-6-specific TNF-α producing CD8+ T-cells in individuals older than 10 years of life (p = 0.033). Additionally, the frequency of HHV-6 specific TNF-α producing CD8+ T-cells positively correlated with the age of the individuals. Linear regression analysis showed a positive relation between age and frequency of HHV-6-specific TNF-α producing CD8+ T-cells.Conclusion: Results indicate that T-cell immune response against HHV-6 is commonly detectable in healthy children and adolescents with higher frequencies of antigen-specific T-cells in older children and adolescents possibly reflecting repeated stimulation by viral persistence and subclinical reactivation

Comparison of the chemical compositions and nutritive values of various pumpkin (Cucurbitaceae) species and parts

Pumpkins have considerable variation in nutrient contents depending on the cultivation environment, species, or part. In this study, the general chemical compositions and some bioactive components, such as tocopherols, carotenoids, and β-sitosterol, were analyzed in three major species of pumpkin (Cucurbitaceae pepo, C. moschata, and C. maxima) grown in Korea and also in three parts (peel, flesh, and seed) of each pumpkin species. C. maxima had significantly more carbohydrate, protein, fat, and fiber than C. pepo or C. moschata (P < 0.05). The moisture content as well as the amino acid and arginine contents in all parts of the pumpkin was highest in C. pepo. The major fatty acids in the seeds were palmitic, stearic, oleic, and linoleic acids. C. pepo and C. moschata seeds had significantly more γ-tocopherol than C. maxima, whose seeds had the highest β-carotene content. C. pepo seeds had significantly more β-sitosterol than the others. Nutrient compositions differed considerably among the pumpkin species and parts. These results will be useful in updating the nutrient compositions of pumpkin in the Korean food composition database. Additional analyses of various pumpkins grown in different years and in different areas of Korea are needed

Eukaryotic translation initiation factor 4AI: a potential novel target in neuroblastoma

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Children suffering from high-risk and/or metastatic NB often show no response to therapy, and new therapeutic approaches are urgently needed. Malignant tumor development has been shown to be driven by the dysregulation of eukaryotic initiation factors (eIFs) at the translation initiation. Especially the activity of the heterotrimeric eIF4F complex is often altered in malignant cells, since it is the direct connection to key oncogenic signaling pathways such as the PI3K/AKT/mTOR-pathway. A large body of literature exists that demonstrates targeting the translational machinery as a promising anti-neoplastic approach. The objective of this study was to determine whether eIF4F complex members are aberrantly expressed in NB and whether targeting parts of the complex may be a therapeutic strategy against NB. We show that eIF4AI is overexpressed in NB patient tissue using immunohistochemistry, immunoblotting, and RT-qPCR. NB cell lines exhibit decreased viability, increased apoptosis rates as well as changes in cell cycle distribution when treated with the synthetic rocaglate CR-1-31-B, which clamps eIF4A and eIF4F onto mRNA, resulting in a translational block. Additionally, this study reveals that CR-1-31-B is effective against NB cell lines at low nanomolar doses (≤20 nM), which have been shown to not affect non-malignant cells in previous studies. Thus, our study provides information of the expression status on eIF4AI in NB and offers initial promising insight into targeting translation initiation as an anti-tumorigenic approach for NB.R35 GM118173 - NIGMS NIH HHS; COMET CBmed - Österreichische Forschungsförderungsgesellschaft; 1 - CSRD VAPublished versio

No Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency

Transplantation and immunomodulatio