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?
OBJECTIVE
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 alphabeta(+) 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-beta, IL-1beta, 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.
De Palma
Raffaele
R
Department of Clinical and Experimental Medicine, Second University of Naples, Napoli, Italy. raffaele.depalma@unina2.it
D'Aiuto
Elena
E
Vettori
Serena
S
Cuoppolo
Pierpaolo
P
Abbate
Gianfranco
G
Valentini
Gabriele
G
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis / Q000276:immunology; D001706:Biopsy; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines