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- Researchers studied the TCRβ and TCRα chain sequences in different thymocyte populations from mouse fetuses and young adults to understand how life-stage affects TCR gene usage.
- They found that the foetal thymocyte populations showed a preference for particular gene segments, exhibiting less diversity and more clonotypic expansions compared to adults, indicating distinct developmental characteristics.
- Interestingly, when young adult thymocytes were treated to synchronize differentiation, they displayed more foetal-like gene usage patterns, suggesting that developmental influences can be manipulated.
Compound-dependent fetal toxicity after in utero exposure to chemotherapy in a pregnant mouse model.
Environ Toxicol Pharmacol
December 2024
Department of Oncology, KU Leuven, Leuven, Belgium; Department of Obstetrics and Gynecology, UZ Leuven, Leuven, Belgium; Gynecologic Oncology, Netherlands Cancer Institute, Anthony Van Leeuwenhoek, Amsterdam, the Netherlands. Electronic address:
Although chemotherapy is integrated in the treatment of second-trimester pregnant cancer patients, its potential cyto- and genotoxicity to fetal tissue remains unknown. To investigate any causal relation between in utero chemotherapy exposure and fetal toxicity, late-gestation pregnant BL6 mice were exposed to vehicle, or one of six chemotherapeutic compounds, used to treat pregnant cases: cyclophosphamide, carboplatin, cisplatin (alkylating agents), epirubicin, doxorubicin (anthracyclines) or paclitaxel (taxane). fetuses were euthanized at gestational day 18.
View Article and Find Full Text PDFA spatial human thymus cell atlas mapped to a continuous tissue axis.
Nature
November 2024
Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus-the Cortico-Medullary Axis-and used it to perform a spatially resolved analysis.
View Article and Find Full Text PDFEarly-life thymectomy leads to an increase of granzyme-producing γδ T cells in children with congenital heart disease.
Nat Commun
November 2024
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring cardiac surgery with concomitant thymectomy that is known to increase disease susceptibility later in life. Studies of γδ T cells, which are one of the dominant T cells in the early fetal human thymus, are rare. Here, we provide a comprehensive analysis of the γδ T cell compartment via flow cytometry and next-generation sequencing in children and infants with CHD, who underwent cardiac surgery shortly after birth.
View Article and Find Full Text PDFAdvanced three-dimensional X-ray imaging unravels structural development of the human thymus compartments.
Commun Med (Lond)
October 2024
Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK.
Background: The thymus, responsible for T cell-mediated adaptive immune system, has a structural and functional complexity that is not yet fully understood. Until now, thymic anatomy has been studied using histological thin sections or confocal microscopy 3D reconstruction, necessarily for limited volumes.
Methods: We used Phase Contrast X-Ray Computed Tomography to address the lack of whole-organ volumetric information on the microarchitecture of its structural components.
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