T cell repertoire in patients with stable scleroderma.
At onset of systemic sclerosis (SSc), T cells have been found to oligoclonally expand in the skin, presumably in response to auto-antigens, but the T cell repertoire has not been evaluated at a later stage. To determine whether a perpetuating immune response contributes to the pathogenesis of stable SSc, the T cell repertoire was analysed in patients with diffuse (d) or limited (l) SSc, and compared to patients with primary Raynaud's phenomenon (RP) or healthy volunteers (Ctrl). The T cell repertoire (total, CD4 or CD8 sorted blood T cells) was analysed by qualitative and quantitative immunoscope (14 BV families analysed) in 11 untreated dSSc and 11 untreated lSSc, 10 RP and 11 Ctrl. To better detect in vivo activated cells, repertoire analysis was also performed on sorted CD4 T cells after in vitro culture with IL-2. In parallel, 6 skin biopsies from SSc patients were analysed. After 7-8 years of disease evolution, SSc patients did not show detectable clonal T cell expansions in the skin, even after tentative expansion from the biopsy with IL-2. Total T cell, sorted CD4 and CD8 T cell repertoires from the blood of patients with SSc did not show significant perturbation as compared to patients with RP and Ctrl. After IL-2 culture for 7 days, blood CD4 T cells from the patients did not preferentially expand as compared to RP and Ctrl. These findings suggest that antigen-driven immune responses may play a lesser role in established SSc than at disease onset.
Tiev
K P
KP
Service de Médecine Interne, Hôpital Saint Antoine, Saint Antoine, Paris, France. kiet.tiev@sat.ap-hop-paris.fr
Abriol
J
J
Burland
M C
MC
Antonelli
D
D
Klatzmann
D
D
Cabane
J
J
Boyer
O
O
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011928:Raynaud Disease / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2