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.