Autoaggressive myocytotoxic T lymphocytes expressing an unusual γ/δ T cell receptor

Polymyositis mediated by γ/δ T cells is a unique disease in which autoaggressive T lymphocytes surround, invade, and destroy muscle fibers. Histochemically, the vast majority of muscle-infiltrating T cells in a patient with polymyositis were reactive with a pan-γ/δ T cell receptor (TCR)-specific monoclonal antibody (TCR-δ1⁺), but unlike >90% of peripheral blood γ/δ T cells, these lymphocytes did not react with Vδ1- or Vγ9-specific antibodies (A13^- and TiγA^-, respectively). Differential reactivity with two different Vδ2-specific monoclonal antibodies (BB3^-/ T_iV-δ2⁺) indicated that the infiltrating T cells express a Vδ2-containing TCR with unusual additional structural features. Using conventional and anchored polymerase chain reaction for the analysis of TCR transcripts, we found a striking predominance of one unusual Vδ2-Jδ3 recombination and one Vγ3-Jγ1 recombination. Both the unusual phenotype (TCR-δ1⁺/A13^-/ TiγA^-/BB3^-/T_iV-δ2⁺) and the dominance of distinct TCR transcripts are compatible with the assumption that one T cell clone, which expresses a Vγ3-Jγ1-Cγ1/Vδ2-Jδ3-Cδ disulfide-linked TCR, dominates among the infiltrating T cells of the polymyositis muscle specimen analyzed.