THE ALPHA-BETA-T-CELL RECEPTOR REPERTOIRE IN INCLUSION-BODY MYOSITIS - DIVERSE PATTERNS OF GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES

Inclusion body myositis (IBM) is one member of a group of disorders known as idiopathic inflammatory myopathies (IIM) in which autoreactive T cells directed against muscle are thought to play a primary role in disease pathogenesis. We have utilized the polymerase chain reaction to determine the pattern of αβ T-cell receptor (TCR) variable (V) gene expression in muscle biopsies from 13 IBM patients. In the majority of biopsies, we detected oligoclonal patterns of TCR V gene expression by muscle-infiltrating lymphocytes; an average of six out of the 22 TCR Vα gene families surveyed and seven out of 24 TCR Vβ gene families surveyed were detected per biopsy. While no TCR Vα gene families were over-represented in our survey, TCR Vβ3 and Vβ6 gene usage was a prominent feature ofIBM muscle biopsies. TCR gene expression was characterized further by analysing the junctional sequence composition of both Vβ3 and Vβ6 clones from muscle biopsies of the IBM patients. A large number of structurally diverse Vβ3 and Vβ6 clonotypes were identified from these patients demonstrating a polyclonal pattern of T cell infiltration. These data, while describing prominent TCR Vβ3 and Vβ6 gene detection, do not suggest that a common antigen-driven T-cell response promotes chronic inflammation in muscle of IBM patients. © 1994 Academic Press. All rights reserved.