Department of Medicine, University of Colorado Denver, 12700 East 19th Avenue, Aurora, CO 80045, USA.
Am J Respir Crit Care Med. 2010 Jun 1;181(11):1241-9. doi: 10.1164/rccm.201001-0025OC. Epub 2010 Mar 18.
Chronic beryllium disease (CBD) is a CD4(+) T cell-mediated disorder characterized by persistent lung inflammation. Naturally occurring regulatory T (T(reg)) cells modulate adaptive immune responses. The role of this T-cell subset in beryllium-induced lung disease is unknown.
The aim of this study was to determine whether dysfunctional T(reg) cells in the lung contribute to the "unchecked" inflammatory response that characterizes CBD.
Using blood and bronchoalveolar lavage (BAL) cells from normal control subjects and individuals with beryllium-induced disease, we determined the frequency and function of naturally occurring T(reg) cells.
A significantly decreased percentage and expression of FoxP3 in BAL CD4(+) T cells from CBD patients compared with beryllium-sensitized subjects was seen, and the percentage of FoxP3-expressing CD4(+) T(reg) cells in BAL inversely correlated with disease severity. In contrast to blood T(reg) cells derived from beryllium-sensitized subjects and patients with CBD that completely suppressed blood responder T-cell proliferation, BAL FoxP3-expressing T(reg) cells from patients with CBD are unable to suppress anti-CD3-mediated BAL T-cell proliferation. Mixing studies showed that blood T(reg) cells are capable of suppressing autologous BAL responder T cells. Conversely, BAL CD4(+) T(reg) cells are incapable of suppressing blood T cells, confirming that the failure of BAL T(reg) cells to suppress T-cell proliferation is caused by a dysfunctional T(reg) cell subset and not by resistance of BAL effector T cells to suppression.
These findings suggest that the deficient and dysfunctional T(reg) cells in the lung of patients with CBD contribute to the persistent inflammatory response in this disease.
慢性铍病（CBD）是一种以 CD4+T 细胞介导的疾病，其特征为持续性肺部炎症。天然存在的调节性 T（Treg）细胞可调节适应性免疫反应。该 T 细胞亚群在铍诱导的肺部疾病中的作用尚不清楚。
本研究旨在确定肺部功能失调的 Treg 细胞是否导致 CBD 中特征性的“不受控制”炎症反应。
使用来自正常对照者和铍诱导疾病患者的血液和支气管肺泡灌洗液（BAL）细胞，我们确定了天然存在的 Treg 细胞的频率和功能。
与铍致敏者相比，CBD 患者的 BAL CD4+T 细胞中 FoxP3 的百分比和表达显著降低，BAL 中表达 FoxP3 的 CD4+Treg 细胞的百分比与疾病严重程度呈反比。与来自铍致敏者和 CBD 患者的血液 Treg 细胞不同，后者完全抑制血液反应性 T 细胞增殖，BAL 中表达 FoxP3 的 Treg 细胞不能抑制抗 CD3 介导的 BAL T 细胞增殖。混合研究表明，血液 Treg 细胞能够抑制自身 BAL 反应性 T 细胞。相反，BAL CD4+Treg 细胞不能抑制血液 T 细胞，证实 BAL Treg 细胞不能抑制 T 细胞增殖是由于功能失调的 Treg 细胞亚群所致，而不是由于 BAL 效应 T 细胞对抑制的抵抗所致。
这些发现表明，CBD 患者肺部功能失调和功能失调的 Treg 细胞导致了该疾病中的持续性炎症反应。
