title: Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time. Studies in repeated muscle biopsies.
abstract: Inclusion body myositis (IBM) is an inflammatory myopathy characterized immunohistologically by prominent invasion of the non-necrotic, MHC-I class antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive CD8+ T cells are recruited specifically to the muscle and play a primary pathogenetic role in the disease, a clonal restriction persisting over time should be anticipated. In this study, we analysed the T-cell receptor (TCR) gene usage by endomysial T lymphocytes in three sequential muscle biopsies from three different IBM patients over a 19-22 month period using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis of the complementarity determining region (CDR3) of the amplified TCRs. We found that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies during a 19-22 month period. The most frequently detected TCRs were the V beta 3, V beta 5.1, V beta 6.7 and V beta 13 gene families, and several of the autoinvasive CD8+ T cells expressed the TCRs V beta 6.7 and V beta 5.1. A restricted usage of the examined V beta 6 gene family was found to persist in the complementarity CDR3 determining region of the autoinvasive T cells over the 22 month period. Identical V beta 6 CDR3 gene arrangements were also found in the multiple muscle biopsies from two of the three IBM patients. The results indicate that in IBM there is a restricted expression of the TCR gene families among the autoinvasive T lymphocytes with homologies in the CDR3 region that persist over the course of the disease. A continuous, antigen-driven T-cell response is prominent in the muscle of patients with IBM.
authors.affiliation: Neuromuscular Disease Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1382, USA.
authors.forename: K
authors.initials: K
authors.lastname: Amemiya
authors.forename: R P
authors.initials: RP
authors.lastname: Granger
authors.forename: M C
authors.initials: MC
authors.lastname: Dalakas
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000276:immunology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; C081278:T cell receptor Vbeta6.7a, human; C113248:T cell receptor peptide Vbeta5.2