The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals.
Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19-38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20-40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups.
Baseline levels of gamma delta (TCRγδ+) T-cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T-cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (-11.1%, p < 0.01), despite similar ratings of perceived exertion.
Elevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise.
TCRγδ+ T-cell baseline levels are elevated in adults with cerebral palsy (CP). The CD8+ T-cell response to exercise was blunted in adults with CP. Exercise intensity is decisive for CD8+ T-cell responses in individuals with CP.
© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

Type 2 immune responses contribute to liver fibrosis in parasite infections, but their role in other liver diseases is less well understood. Here, we aimed at unravelling mechanisms involved in T helper 2 (Th2) T-cell polarization, activation, and recruitment in human liver fibrosis and cirrhosis.
Tissues, cells, and serum from human livers were analyzed using quantitative reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, fluorescence in situ hybridization, immunostaining, flow cytometry, and various functional in vitro assays. Cellular interactions and soluble mediators involved in T-cell polarization and recruitment were studied, as well as their effect on hepatic stellate cell (HSC) activation, proliferation, and extracellular matrix synthesis.
In human liver fibrosis, a stage-dependent increase in Th2-related transcription factors, Th2 cytokines, and trans-acting T-cell-specific transcription factor-expressing T cells was observed, and was highest in cirrhotic livers. The alarmin interleukin (IL)33 was found to be increased in livers and sera from patients with cirrhosis, to act as a chemotactic agent for Th2 cells, and to induce type 2 polarization of CD4+ T cells. Oval cells, liver sinusoidal endothelial cells, intrahepatic macrophages, and migrating monocytes were identified as sources of IL33. IL33-activated T cells, but not IL33 alone, induced HSC activation, as shown by Ki67 and α-smooth muscle actin staining, increased collagen type I alpha 1 chain messenger RNA expression, and wound healing assays. The profibrotic effect of IL33-activated T cells was contact-independent and could be antagonized using monoclonal antibodies against IL13.
In patients with chronic liver disease, the alarmin IL33 promotes the recruitment and activation of CD4+ T cells with Th2-like properties, which activate paracrine HSC in an IL13-dependent manner and promotes fibrogenesis.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies.

Aim Low physical activity alters immune function and increases the risk of developing chronic inflammation. This cross-sectional study aimed at determining the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing (TD) individuals. Method Blood samples from 12 individuals with CP and 17 TD were collected before, immediately after, and one hour following 45 minutes of Frame Running or running, respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model ANOVA was utilized to investigate immune cell responses to exercise across groups. Results Baseline levels of TCRγδ+ T-cells were significantly higher in the individuals with CP. Several cell populations showed significant changes after exercise in both CP and TD groups. CD8+ T-cells were only significantly elevated immediately after exercise in the TD participants. Individuals with CP exhibited significantly lower heart rates, despite similar ratings of perceived exertion. Interpretation Elevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise. What this paper adds This is the first study addressing immune cells in adults with CP TCRγδ+ T-cell baseline levels are elevated in adults with CP The CD8+ T-cell response to exercise was blunted in adults with CP Exercise intensity is decisive for CD8+ T-cell responses in individuals with CP

Varicella caused by the primary infection of varicella-zoster virus (VZV) exerts a considerable disease burden globally. Current varicella vaccines consisting of the live-attenuated vOka strain of VZV are generally safe and effective. However, vOka retains full neurovirulence and can establish latency and reactivate to cause herpes zoster in vaccine recipients, raising safety concerns. Here, we rationally design a live-attenuated varicella vaccine candidate, v7D. This virus replicates like wild-type virus in MRC-5 fibroblasts and human PBMCs, the carrier for VZV dissemination, but is severely impaired for infection of human skin and neuronal cells. Meanwhile, v7D shows immunogenicity comparable to vOka both in vitro and in multiple small animal species. Finally, v7D is proven well-tolerated and immunogenic in nonhuman primates. Our preclinical data suggest that v7D is a promising candidate as a safer live varicella vaccine with reduced risk of vaccine-related complications, and could inform the design of other herpes virus vaccines.
© 2022. The Author(s).