The mechanisms of T cell vaccination (TCV) are still unclear, especially the molecular interactions for recognition of autoreactive T cells by the immune system. Here we investigated the role of CD28:B7 interaction in TCV-induced protection in the murine EAE model. We demonstrate that there is increased expression of both B7-1 and B7-2 on autoreactive Th1 cells compared to Th2 cells. Blockade of B7 on the vaccinating autoreactive T cell surface or blockade of CD28 in recipient mice reduced the protective effect of TCV. Furthermore, we showed that TCV significantly inhibited Ag-specific CD4 and CD8 T cell proliferation and decreased Ag-specific IFN-gamma production by CD4 T cells in mice undergoing TCV, and blocking of B7 on the surface of vaccinating T cells reduced this inhibition on Ag-specific CD4 and CD8 T cell proliferation, more significantly on Ag-specific CD4 T cell proliferation. These data indicated that B7 expression on autoreactive T cells is necessary for the recognition of autoreactive T cells by the immune system and subsequent protection from EAE in mice undergoing TCV.
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http://dx.doi.org/10.1002/eji.200636971 | DOI Listing |
ACR Open Rheumatol
January 2025
ISAR Bioscience GmbH, Planegg, Germany.
Objective: Rheumatoid arthritis (RA) is characterized by circulating anti-cyclic citrullinated peptide (CCP) autoantibodies (ACPAs), resulting in inflammation of the joints and other organs. We have established novel assays to assess immune cell subpopulations, including citrullinated antigen-specific (CAS) autoreactive B and T lymphocytes, in patients with RA.
Methods And Results: We found that activated CD25 T cells were markedly increased in patients with RA compared to healthy controls.
Kidney Int
January 2025
Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia. Electronic address:
Anti-glomerular basement membrane (anti-GBM) disease is accompanied by insufficient antigen-specific T regulatory cells (Tregs) and clonally expanded antigen-specific T conventional cells (Tconvs). In particular, this applied to the immunodominant T cell auto- epitope of type IV collagen, α3(IV)NC1135-145 , presented by HLA-DR15. Here, we investigated whether Tregs engineered to express GBM-T cell receptors (TCR) specific for α3(IV)NC1135- 145 better suppress autoimmunity.
View Article and Find Full Text PDFBr J Haematol
January 2025
Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease resulting from a cytotoxic T-cell-mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding the T-cell repertoire alterations in AA, identifying specific pathogenic T cells in AA patients has remained elusive, primarily due to the unknown antigenic targets of the autoimmune attack. In this review, we will synthesize findings from several decades of research to critically evaluate the current knowledge on T-cell repertoires in AA.
View Article and Find Full Text PDFJ Autoimmun
January 2025
Division of Haematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA; Pediatric Haematology and Oncology, The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA; The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address:
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated B cell activation, autoantibody production, and nephritis. B cell activating factor (BAFF) overexpression enhances autoreactive B-cell survival, driving autoimmunity. BAFF specific belimumab and CD20 specific rituximab antibodies are used for SLE therapy but are not curative, highlighting the need for alternative B cell depletion therapies.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.
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