Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic beta cells by T lymphocytes. Prediction of cell-mediated autoimmune diseases by direct detection of autoreactive T cells in peripheral blood has proved elusive, in part because of their low frequency and reduced avidity for peptide MHC ligands. This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.
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http://dx.doi.org/10.1172/JCI16409 | DOI Listing |
J Clin Immunol
January 2025
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.
View Article and Find Full Text PDFNat Immunol
January 2025
Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.
Here we analyzed the relative contributions of CD4 regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8 regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4 and CD8 regulatory T cells. Using CRISPR-Cas9 gene editing, we were able to achieve a reduction of ~90-95% in the expression of these genes.
View Article and Find Full Text PDFRheumatol Immunol Res
December 2024
Department of Toxicology, School of Public Health, Peking University; Peking China.
Autoimmune diseases arise from immune system dysfunction that immune cells mistakenly attack the body's own tissues, resulting in systemic disorders or localized lesions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Autoreactive B cells play a critical role in the pathogenesis of many autoimmune diseases and B cell depletion using anti-CD20 monoclonal antibody (mAb) has been shown to effectively mitigate disease progression in both preclinical and clinical studies. Recently, bispecific antibody (bsAb) targeting CD20/CD3 have demonstrated substantial clinical benefits in the treatment of various hematologic malignancies.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Cerebro, Emoción y Conducta, School of Medicine, Universidad de las Américas (UDLA), Quito 170124, Ecuador.
Paraneoplastic cerebellar degeneration (PCD) is a rapidly progressive, immune-mediated syndrome characterized by the degeneration of Purkinje cells, often associated with the presence of antibodies targeting intracellular antigens within these cells. These autoantibodies are implicated in the induction of cytotoxicity, leading to Purkinje cell death, as demonstrated in in vitro models. However, the precise roles of antibodies and T lymphocytes in mediating neuronal injury remain a subject of ongoing research, with T cells appearing to be the main effectors of cerebellar injury.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, China.
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody-mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high-throughput data, except for the belated emergence of autoreactive antibodies.
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