In type 1 diabetes (T1D), a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8 T cells are the main cell type found in the insulitic lesion, and CD8 T cells reactive against β-cell antigens have been detected in peripheral blood and in the pancreas of patients with short- or long-term disease. In the Diabetes Virus Detection (DiViD) study, researchers collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset T1D. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T-cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8 T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We also show the heterogeneity of islet distribution and CD8 T-cell infiltration. Our findings contribute to the current limited existing knowledge of T-cell reactivity in the pancreas of donors with recent-onset T1D and indicate that antigen-specific therapies directed toward preproinsulin could have high clinical impact.
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http://dx.doi.org/10.2337/db20-0908 | DOI Listing |
Elife
December 2024
Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
Since the precursor frequency of naive T cells is extremely low, investigating the early steps of antigen-specific T cell activation is challenging. To overcome this detection problem, adoptive transfer of a cohort of T cells purified from T cell receptor (TCR) transgenic donors has been extensively used but is not readily available for emerging pathogens. Constructing TCR transgenic mice from T cell hybridomas is a labor-intensive and sometimes erratic process, since the best clones are selected based on antigen-induced CD69 upregulation or IL-2 production in vitro, and TCR chains are polymerase chain reaction (PCR)-cloned into expression vectors.
View Article and Find Full Text PDFSci Immunol
January 2025
Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.
View Article and Find Full Text PDFPLoS One
January 2025
Transplant Group, La Paz University Hospital Health Research Institute (IdiPAZ), Madrid, Spain.
Background: Intestinal transplantation (ITx) represents the only curative option for patients with irreversible intestinal failure. Nevertheless, its rejection rate surpasses that of other solid organ transplants due to the heightened immunological load of the gut. Regulatory T-cells (Tregs) are key players in the induction and maintenance of peripheral tolerance, suggesting their potential involvement in modulating host vs.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Tumor-associated macrophages (TAMs) are commonly considered accomplices in tumorigenesis and tumor development. However, the precise mechanism by which tumor cells prompt TAMs to aid in evading immune surveillance remains to be further investigated. Here, it is elucidated that tumor-secreted galectin-1 (Gal1) conferred immunosuppressive properties to TAMs.
View Article and Find Full Text PDFParasitol Res
January 2025
Facultad de Química, Universidad Autónoma de Yucatán (UADY), Calle 43 S/N entre calle 96 y calle 40 Colonia Inalámbrica, Mérida, Yucatán, C.P. 97069, Mexico.
Chagas disease is a chronic infection caused by the protozoan parasite, Trypanosoma cruzi, with limited benefits of the currently available anti-parasitic chemotherapeutic approaches to halt the progression of heart disease. Recombinant TSA-1-C4 and Tc24-C4 proteins have been developed as promising antigen candidates for therapeutic vaccines, leading to propose them in combination as a bivalent recombinant protein strategy. In this study, we evaluated the immunomodulatory effect of the combined TSA-1-C4 and Tc24-C4 recombinant proteins by in vitro assays using murine macrophages.
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