ArticleProceedings of the National Academy of Sciences of the United States of America2003
Clonal tracking of autoaggressive T cells in polymyositis by combining laser microdissection, single-cell PCR, and CDR3-spectratype analysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 110 citations in OpenAlex.
- An update on the pathogenesis of idiopathic inflammatory myopathies.Current opinion in rheumatology · 2025Review
- Article
- Inflammatory Myopathies and Autoimmune Gluten-related Disorders: A Scoping Review of Pathophysiological Interconnections and Hypothesis.Recent advances in inflammation & allergy drug discovery · 2025Article
- Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging.International journal of molecular sciences · 2024Review
- Antigen-driven T cell-macrophage interactions mediate the interface between innate and adaptive immunity in histidyl-tRNA synthetase-induced myositis.Frontiers in immunology · 2023Article
- Inflammatory myopathies: update on diagnosis, pathogenesis and therapies, and COVID-19-related implications.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2020Review
- Polymyositis and dermatomyositis - challenges in diagnosis and management.Journal of translational autoimmunity · 2019Article
- Current Classification and Management of Inflammatory Myopathies.Journal of neuromuscular diseases · 2018Review
- Human CD8(+) T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV-1 recognize both epitopes.Journal of cellular and molecular medicine · 2016Article
- FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord.The EMBO journal · 2015Article
- Long-term efficacy of alemtuzumab in polymyositis.Rheumatology (Oxford, England) · 2015Article
- Detection of clonal T-cell-receptor (TCR) Vbeta rearrangements in explanted dilated cardiomyopathy hearts by semi-nested PCR, GeneScan, and direct sequencing.Medical science monitor basic research · 2013Article
- T cells in myositis.Arthritis research & therapy · 2012Review
- Inclusion body myositis: laser microdissection reveals differential up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers.The American journal of pathology · 2011Article
- Pathogenesis, classification and treatment of inflammatory myopathies.Nature reviews. Rheumatology · 2011Review
- Immunotherapy of myositis: issues, concerns and future prospects.Nature reviews. Rheumatology · 2010Review
- Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis.Clinical and experimental immunology · 2010Article
- Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes.British journal of cancer · 2009Article
- Novel approaches for identifying target antigens of autoreactive human B and T cells.Seminars in immunopathology · 2009Review
- Advances in the immunobiology and treatment of inflammatory myopathies.Current rheumatology reports · 2007Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clonal expansions of CD8+ T cells have been identified in muscle and blood of polymyositis patients by PCR techniques, including T cell receptor (TCR) complementarity-determining region (CDR)3 length analysis (spectratyping). To examine a possible pathogenic role of these clonally expanded T cells, we combined CDR3 spectratyping with laser microdissection and single-cell PCR of individual myocytotoxic T cells that contact, invade, and destroy a skeletal muscle fiber. First, we screened cDNA from muscle biopsy specimens by CDR3 spectratyping for expanded TCR beta chain variable region (BV) sequences. To pinpoint the corresponding T cells in tissue, we stained cryostat sections with appropriate anti-TCR BV mAbs, isolated single BV+ T cells that directly contacted or invaded a muscle fiber by laser-assisted microdissection, and amplified their TCR BV chain sequences from rearranged genomic DNA. In this way, we could relate the oligoclonal peaks identified by CDR3-spectratype screening to morphologically characterized microdissected T cells. In one patient, a large fraction of the microdissected T cells carried a common TCR-BV amino acid CDR3 motif and conservative nucleotide exchanges in the CDR3 region, suggesting an antigen-driven response. In several cases, we tracked these T cell clones for several years in CD8+ (but not CD4+) blood lymphocytes and in two patients also in consecutive muscle biopsy specimens. During immunosuppressive therapy, oligoclonal CDR3-spectratype patterns tended to revert to more polyclonal Gaussian distribution-like patterns. Our findings demonstrate that CDR3 spectratyping and single-cell analysis can be combined to identify and track autoaggressive T cell clones in blood and target tissue. This approach should be applicable to other inflammatory and autoimmune disorders.
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