RESUMEN
The balance in the production and release of cytokines "Th1/Th2" or "Th17" or "regulatory T" is one of the key events in the pathogenesis of systemic sclerosis (SSc). Specifically, the Th2 cytokine response, characterized by the production of IL-4, IL-10 and TGF-ß, leads to tissue fibrosis in patients with SSc. Many studies have shown the importance of analyzing the levels of cytokines as diagnostic or prognostic markers in the blood or in situ in patients with SSc. The restoration of the Th1/Th2/Th17/Treg balance will contribute to the effectiveness of treatment and the use of cytokine modulators may therefore be considered in developing new therapeutic approaches.
Asunto(s)
Citocinas/metabolismo , Esclerodermia Sistémica/metabolismo , Comunicación Celular/fisiología , Citocinas/sangre , Citocinas/clasificación , Citocinas/fisiología , Humanos , Modelos Biológicos , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/etiología , Esclerodermia Sistémica/inmunología , Células TH1/metabolismo , Células TH1/fisiología , Balance Th1 - Th2 , Células Th2/metabolismo , Células Th2/fisiologíaRESUMEN
The present pilot study aims to evaluate the frequency and the function of regulatory T (Treg) cells in patients with diffuse cutaneous SSc (dcSSc) before and after autologous hematopoietic SCT (aHSCT). Peripheral blood lymphocytes from seven dcSSc patients were analyzed before and 24 months after aHSCT and were compared with those from seven healthy donors (controls). Immunophenotyping of CD4(+)CD25(high)FoxP3(+) natural Treg (nTreg), CD4(+)CD25(+)TGF-ß(+) and CD4(+)CD25(+)IL-10(+) adaptive Treg (aTreg) cell subsets was performed using four-color flow cytometry. Treg-suppressive capability was measured after coculture with autologous T effector cells by evaluation of T-cell proliferation using (3)H-thymidine incorporation. Peripheral CD4(+)CD25(high)FoxP3(+) (2±0.5 vs 4.2±1.1, P<0.01), CD4(+)CD25(+)TGF-ß(+) (6.9±1.8 vs 14.6±5.0, P<0.05) and CD4(+)CD25(+)IL-10(+) (10.7±0.5 vs 16.1±3.2, P<0.01) Tregs as well as CD4(+)CD25(high)CD127(low) Tregs suppressive capacity (P<0.05) were decreased in dcSSc patients vs controls. After aHSCT (n=7), the percentages of CD4(+)CD25(high)FoxP3(+) (4.1±1.8) and CD4(+)CD25(+)IL-10(+) (15.7±2.2) Treg cells and the suppressive activity of CD4(+)CD25(high)CD127(low) were restored to the levels in controls. The decreased frequency and the functional defect of peripheral Treg cells from patients with dcSSc are reversed following aHSCT to reach those observed in controls. This pilot study brings evidence of an effective restoration of nTreg and aTreg subsets, and recovery of nTreg suppressive function following aHSCT.