Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time - Studies in repeated muscle biopsies

Inclusion body myositis (IBM) is an inflammatory myopathy characterized imm unohistologically by prominent invasion of the non-necrotic, MHC-I class an tigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasi ve CD8+ T cells are recruited specifically to the muscle and play a primary pathogenetic role in the disease, a clonal restriction persisting over tim e should be anticipated. In this study, we analysed the T-cell receptor (TC R) gene usage by endomysial T lymphocytes in three sequential muscle biopsi es from three different IBM patients over a 19-22 month period using immuno histochemistry, reverse transcription-polymerase chain reaction (RT-PCR) an d 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 frequent ly detected TCRs were the V beta 3, V beta 5.1, V beta 6.7 and V beta 13 ge ne families, and several of the autoinvasive CB8+ T cells expressed the TCR s V beta 6.7 and V beta 5.1. A restricted usage of the examined V beta 6 ge ne family was found to persist in the complementarity CDR3 determining regi on 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 fro m 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 l ymphocytes with homologies in the CDR3 region that persist over the course of the disease. a continuous, antigen-driven T-cell response is prominent i n the muscle of patients with IBM.