Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study
Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study
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DOI：
10.1038/bmt.2013.202
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发表时间：
2014-03-01
影响因子：
4.8
通讯作者：
Michel, L.
中科院分区：
文献类型：
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作者：
Baraut, J.;Grigore, E. L.;Michel, L.
本初步研究旨在评估弥漫性皮肤 SSc (dcSSc) 患者在自体造血 SCT (aHSCT) 前后的调节性 T (Treg) 细胞频率和功能。在 aHSCT 之前和之后 24 个月对 7 名 dcSSc 患者的外周血淋巴细胞进行了分析，并与 7 名健康捐赠者（对照）的外周血淋巴细胞进行了比较。使用四色流式细胞术对 CD4(+)CD25(high)FoxP3(+) 天然 Treg (nTreg)、CD4(+)CD25(+)TGF-β(+) 和 CD4(+)CD25(+)IL-10(+) 适应性 Treg (aTreg) 细胞亚群进行免疫表型分析。在与自体T效应细胞共培养后，通过使用3H-胸苷掺入评估T细胞增殖来测量Treg抑制能力。外周 CD4_CD25highFoxP3_（2 +/- 0.5 vs 4.2 +/- 1.1，P < 0.01）、CD4_CD25(+)TGF-beta(+)（6.9 +/- 1.8 vs 14.6 +/- 5.0，P < 0.05）和 CD4(+)CD25(+)IL-10(+) (10.7 +/- 0.5 vs 16.1 +/- 3.2，P < 0.01) 与对照组相比，dcSSc 患者的 Tregs 以及 CD4(+)CD25(高)CD127(低)Treg 抑制能力 (P < 0.05) 均降低。 aHSCT（n=7）后，CD4（+）CD25（高）FoxP3（+）（4.1+/-1.8）和CD4（+）CD25（+）IL-10（+）（15.7+/-2.2）Treg细胞的百分比和CD4（+）CD25（高）CD127low的抑制活性恢复至对照水平。 dcSSc 患者外周 Treg 细胞的频率降低和功能缺陷在 aHSCT 后得到逆转，达到对照组观察到的水平。这项初步研究提供了 nTreg 和 aTreg 亚群有效恢复以及 aHSCT 后 nTreg 抑制功能恢复的证据。
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-beta(+) 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 3H- thymidine incorporation. Peripheral CD4_CD25highFoxP3_ (2 +/- 0.5 vs 4.2 +/- 1.1, P < 0.01), CD4_CD25(+)TGF-beta(+) (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)CD127low 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.