γδ T cell receptor gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies

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Abstract
SUMMARY: Autoreactive αβ T cells have been implicated as playing a primary pathogenic role in a group of diseases characterized by chronic muscle inflammation known as the idiopathic inflammatory myopathies (IIM). γδ T cells, a distinct and enigmatic class of T cells, play a less certain role in a variety of human autoimmune diseases including the IIM. In an attempt to understand the significance of γδ T cells in the IIM, we utilized a sensitive polymerase chain reaction (PCR) technique to evaluate γδ T cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis). γδ TCR gene expression was not detected in 36 specimens, the majority of muscle biopsies surveyed. γδ TCR gene expression by muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous patients. We further analysed the junctional sequence composition of the Vγ3 and Vδ1 transcripts, whose expression was prominent among γδ positive patients. DNA sequence analysis of Vγ3 amplification products from two patients revealed the presence of several productively rearranged transcripts with amino acid sequence similarities within the Vγ3-N-Jγ junctional domain. No amino acid sequence similarities were evident within the Vδ-N-Dδ-N-Jδ region of Vδ1 transcripts amplified from four patients, although a distinct and dominant clonotype was detected from each patient. Our cumulative data suggest that unlike αβ T cells, γδ T cells do not play a prominent pathologic role in the IIM. In fact, the sporadic nature of γδ TCR gene expression detected among these patients implies that γδ T cell infiltration, when it occurs, is a secondary event perhaps resulting from non-specific inflammatory processes.