Blood T-lymphocyte functions were studied in 167 healthy adults (age range 19-91 years). Lymphocyte DNA synthesis induced by concanavalin A, pokeweed mitogen and PPD antigen declined with age while the spontaneous DNA synthesis remained essentially unchanged. Relative and total T-cell counts but not total lymphocyte counts were moderately decreased in elderly persons. The lymphocyte response to mitogens correlated with the PPD-induced activation in vitro. Lymphocyte and T-cell counts did not show any association with the response to mitogens and antigen. A few subjects were tested on several occasions during 2-7 years confirming a good reproducibility of the techniques employed. Thus ageing is associated with diminished number of T-cells and impairment of lymphocyte activation by T-cell mitogens and PPD antigen. The clinical importance of this general age-related T-cell deficiency remains largely unresolved.
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http://dx.doi.org/10.1111/j.1600-0609.1982.tb02119.x | DOI Listing |
Nat Commun
January 2025
Department of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma.
View Article and Find Full Text PDFSci Data
January 2025
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
The distinctive characteristics of an individual's T cell receptor repertoire are crucial in recognizing and responding to a diverse array of antigens, contributing to immune specificity and adaptability. The repertoire, famously vast due to a series of cellular mechanisms, can be quantified using repertoire sequencing. In this study, we sampled the repertoire of 85 women: ovarian cancer patients (OC) and healthy donors (HD), generating a dataset of T cell clones and their abundance.
View Article and Find Full Text PDFNat Commun
January 2025
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.
Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.
View Article and Find Full Text PDFSci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P. R. China.
Cancer immunotherapies rely on CD8 cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors.
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