Vγ9+ γδ T cells in systemic sclerosis patients are numerically and functionally preserved and induce fibroblast apoptosis

Vδ1 expressing γδ T cells are oligoclonally expanded in systemic sclerosis (SSc) (scleroderma) and thought to play an immunopathogenic role, whereas that of Vγ9+ γδ T cells is unclear. In studies of 16 patients and 16 healthy controls (HCs) we found that whereas the percent of Vδ1+ γδ T cells was significantly elevated among the peripheral blood T cells in patients without radiographic evidence of interstitial lung disease (n=7), Vγ9+ T cells were equally and persistently represented irrespective of pulmonary disease or cyclophosphamide treatment, at levels similar to healthy controls. Furthermore, ex vivo triggering of patient Vγ9+ T cells with isopentenyl pyrophosphate plus interleukin-2-induced dose-dependent expansion, secretion of tumor necrosis factor α, and contact-dependent apoptosis of co-cultured fibroblasts similarly to Vγ9+ T cells of controls. Fully functional Vγ9+ T cells persisting in the peripheral blood of patients with progressive systemic sclerosis could potentially play an immunopathogenic role in vivo by secreting cytokines and inducing death of fibroblasts in a contact-dependent manner when activated by specific antigens.