Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease
Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease
复制标题
DOI：
10.1016/s0140-6736(04)15592-x
复制
发表时间：
2004-02-21
期刊：
影响因子：
168.9
通讯作者：
Robinson, DS
中科院分区：
文献类型：
--
作者：
Ling, EM;Smith, T;Robinson, DS
背景 过敏性疾病十分常见且患病率不断上升，是过敏原激活辅助性 T (Th) 2 细胞的结果。 CD4+CD25+调节性T细胞在体外抑制T细胞活化并防止疾病动物模型中的病理发现。我们的目的是研究CD4+CD25+T细胞对过敏反应的抑制量是否与特应性和过敏性疾病有关。方法从三组供体中分离血液CD4+CD25+和CD4+CD25-T细胞：非特应性个体；没有任何症状的特应性患者；花粉热患者在草花粉季节期间和之外进行了研究。我们研究了来自这些供体的 CD25+ T 细胞在体外抑制过敏原刺激的 T 细胞增殖和细胞因子产生的能力。结果发现，来自非特应性供体的 CD4+CD25+ T 细胞通过其自身的过敏原刺激的 CD4+CD25- T 细胞抑制了增殖和白细胞介素 5 的产生。来自特应性供体的 CD4+CD25+ T 细胞对增殖的抑制显着降低 (p=0.0012)，并且在花粉季节期间从花粉热患者中分离的 CD4+CD25+ T 细胞的抑制作用甚至更大 (p=0.0003)。在花粉热患者中，反季节抑制仍然低于来自非特应性供体的调节细胞所观察到的抑制。 解释 过敏性疾病可能是由于调节性 CD4+CD25+ T 细胞和效应 Th2 细胞的过敏原激活之间的不适当平衡所致。这种不平衡可能是由于调节性 T 细胞的抑制缺陷造成的，或者强激活信号可以克服这种调节。增强调节性 T 细胞反应并减少 Th2 细胞活化的治疗可能有助于预防和治疗过敏性疾病。
Background Allergic diseases are frequent and rising in prevalence, and result from activation of T-helper (Th) 2 cells by allergens. CD4+CD25+ regulatory T cells suppress T-cell activation in vitro and prevent pathological findings in animal models of disease. We aimed to investigate whether the amount of inhibition of allergic responses by CD4+CD25+ T cells was related to atopy and allergic disease.Methods Blood CD4+CD25+ and CD4+CD25- T cells were isolated from three groups of donors: non-atopic individuals; those atopic with no present symptoms; and patients with hayfever studied during and out of the grass-pollen season. We investigated the ability of CD25+ T cells from these donors to suppress allergen-stimulated T-cell proliferation and cytokine production in vitro.Findings CD4+CD25+ T cells from non-atopic donors suppressed proliferation and interleukin 5 production by their own allergen-stimulated CD4+CD25- T cells. Inhibition of proliferation by CD4+CD25+ T cells from atopic donors was significantly reduced (p=0.0012), and was even more diminished by CD4+CD25+ T cells isolated from patients with hayfever during the pollen season (p=0.0003). In patients with hayfever, out-of-season suppression remained less than that seen by regulatory cells from non-atopic donors.Interpretation Allergic disease can result from an inappropriate balance between allergen activation of regulatory CD4+CD25+ T cells and effector Th2 cells. This imbalance could result from a deficiency in suppression by regulatory T cells or strong activation signals could overcome such regulation. Treatment to enhance regulatory T-cell responses, in concert with reduction of Th2 cell activation, might be useful in prevention and treatment of allergic disease.