Peripheral T cells from patients with early systemic sclerosis kill autologous fibroblasts in co-culture: is T-cell response aimed to play a protective role?

Abstract Objectives. Oligoclonal T-cell infiltrates have been detected in the skin of patients with early dcSSc. Peripheral T cells from patients with early dcSSc co-cultured with autologous fibroblasts have been found to expand the same T-cell clonotypes found in the affected skin. Here, we characterize oligoclonally expanded T lymphocytes and investigate functional changes occurring in early-dcSSc co-cultured T lymphocytes and fibroblasts. Methods. Peripheral T lymphocytes from five patients with early (<3-year duration) dcSSc were co-cultured with the autologous fibroblasts obtained by punch biopsy of involved skin. Results. T-cell clonotypes expanded in co-cultures were found to be ab+ and HLA-DR+, and to promote the apoptosis of autologous fibroblasts. Fibroblasts up-regulated Fas and underwent apoptosis that paired with the expression of Fas ligand (Fasl) on CD4+ T cells. Finally, the addition of a blocking anti-Fas antibody to the co-cultures resulted in a marked reduction of fibroblast apoptosis, suggesting a critical role of Fas/Fasl engagement in mediating apoptosis in co-cultured fibroblasts. In the co-culture supernatants, we found TGF-b, IL-1b, IL-6 and IL-8, cytokines that are known to promote fibrosis in SSc. The same results were registered in each co-culture. Conclusions. Taken together, these data suggest that T-cell response in SSc may also represent an attempt of the immune system to kill fibroblasts, cells likely expressing (auto)antigens, although the overall outcome of the T-cell response contributes to sustain inflammatory loops leading to fibrosis