Exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstrate that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, it was determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) than HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426990 | PMC |
| http://dx.doi.org/10.3109/1547691X.2014.917748 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BRAF pediatric low-grade gliomas frequently transform into high-grade gliomas (HGG) and poorly respond to chemotherapy, resulting in high mortality. Although combined BRAF and MEK inhibition (BRAFi+MEKi) outperforms chemotherapy, ∼70% of BRAF HGG patients are therapy resistant and undergo unbridled tumor progression. BRAF glioma have an immune-rich microenvironment suggesting that they could be responsive to immunotherapy but effects of BRAFi+MEKi on anti-tumor immunity are unclear.
View Article and Find Full Text PDFNovel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease.
Front Immunol
September 2024
Department of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Type 1 diabetes (T1D) is an autoimmune disease with a strong chronic inflammatory component. One possible strategy for the treatment of T1D is to stimulate the regulatory arm of the immune response, i.e.
View Article and Find Full Text PDFComprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer.
Microbes Infect
May 2024
Department of Gastrointestinal Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China. Electronic address:
Background: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC.
Methods: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC.
Innate Lymphoid Cells in Bladder Cancer: From Mechanisms of Action to Immune Therapies.
Cancer Immunol Res
February 2024
Department of Urology, University of Texas Health San Antonio, San Antonio, Texas.
Bladder tumors have a high mutational burden and tend to be responsive to immune therapies; however, response rates remain modest. To date, immunotherapy in bladder cancer has largely focused on enhancing T-cell immune responses in the bladder tumor microenvironment. It is anticipated that other immune cells, including innate lymphoid cells (ILC), which play an important role in bladder oncogenesis and tumor suppression, could be targeted to improve response to existing therapies.
View Article and Find Full Text PDFImmunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy.
JCI Insight
July 2023
Department of Immunology and.
Article Synopsis
- T cells detect mutated peptides from tumors that show up on MHC, playing a crucial role in the immune system's ability to fight cancer.
- Researchers are now using new systems to identify these tumor-specific neo-epitopes, which have been hard to pinpoint in human tumors.
- Their study found varying levels of antigenicity in different sarcomas, suggesting that highly antigenic tumors with weak T cell responses could be targeted effectively with T cell-enhancing immunotherapy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!