Vgamma9+ gammadelta T cells in systemic sclerosis patients are numerically and functionally preserved and induce fibroblast apoptosis.
Vdelta1 expressing gammadelta T cells are oligoclonally expanded in systemic sclerosis (SSc) (scleroderma) and thought to play an immunopathogenic role, whereas that of Vgamma9+ gammadelta T cells is unclear. In studies of 16 patients and 16 healthy controls (HCs) we found that whereas the percent of Vdelta1+ gammadelta T cells was significantly elevated among the peripheral blood T cells in patients without radiographic evidence of interstitial lung disease (n=7), Vgamma9+ 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 Vgamma9+ T cells with isopentenyl pyrophosphate plus interleukin-2-induced dose-dependent expansion, secretion of tumor necrosis factor alpha, and contact-dependent apoptosis of co-cultured fibroblasts similarly to Vgamma9+ T cells of controls. Fully functional Vgamma9+ 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.
Bendersky
Anna
A
Laboratory for Immunoregulation, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
Markovits
Noa
N
Bank
Ilan
I
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521522:T-cell receptor Vgamma9, human