Expansion of selected Vδ1⁺ γδ T cells in systemic sclerosis patients

We have previously shown an increased percentage of γδ T cells expressing the TCR Vδ1 gene segment in the peripheral blood and bronchoalveolar lavage fluid of patients with systemic sclerosis (SSC). To estimate clonality of these Vδ1⁺ T cells, the diversity of Vδ1 junctional regions (V-D-I) was examined using a reverse transcriptase-PCR to amplify TCR δ-chain transcripts isolated from PBMC, lung, esophagus, stomach, or skin of patients and controls. Limited diversity of Vδ1-Jδ junctional regions in SSC patients was demonstrated by comparing the size distribution of PCR-amplified junctional region cDNA from patients with that of controls. Sequence analyses confirmed that Vδ1-Jδ junctional regions from the blood of SSc patients had less diversity than those from controls, in that a significantly higher proportion of sequences were repeated in patients (54.4 vs 19.4% in controls). Evidence for selection of the Vδ1⁺ T cells in the tissues of SSC patients came from the findings that the same Vδ1-Jδ junctional sequences persisted in an individual patient over time and that identical junctional sequences were isolated from multiple sites. Analysis of deduced amino acid sequences revealed two clusters of similarities among the junctional regions from patients. These data suggest that expansion of Vδ1⁺ γδ T cells may be Ag driven in SSC patients.