Marinić Igor, Gagro Alenka, Rabatić Sabina
Imunoloski zavod, Zagreb, Hrvatska.
Acta Med Croatica. 2006 Dec;60(5):447-56.
Regulatory T-cells are a subset of T cells that have beene extensively studied in modern immunology. They are important for the maintenance of peripheral tolerance, and have an important role in various clinical conditions such as allergy, autoimmune disorders, tumors, infections, and in transplant medicine. Basically, this population has a suppressive effect on the neighboring immune cells, thus contributing to the local modulation and control of immune response. There are two main populations of regulatory T cells - natural regulatory T cells, which form a distinct cellular lineage, develop in thymus and perform their modulatory action through direct intercellular contact, along with the secreted cytokines; and inducible regulatory T cells, which develop in the periphery after contact with the antigen that is presented on the antigen presenting cell, and their primary mode of action is through the interleukin 10 (IL-10) and transforming growth factor beta (TGF-alpha) cytokines. Natural regulatory T cells are activated through T cell receptor after contact with specific antigen and inhibit proliferation of other T cells in an antigen independent manner. One of the major difficulties in the research of regulatory T cells is the lack of specific molecular markers that would identify these cells. Natural regulatory T cells constitutively express surface molecule CD25, but many other surface and intracellular molecules (HLA-DR, CD122, CD45RO, CD62, CTLA-4, GITR, PD-1, Notch, FOXP3, etc.) are being investigated for further phenotypic characterization of these cells. Because regulatory T cells have an important role in establishing peripheral tolerance, their importance is manifested in a number of clinical conditions. In the IPEX syndrome (immunodysregulation, polyendocrinopathy and enteropathy, X-linked), which is caused by mutation in Foxp3 gene that influences the development and function of regulatory T cells, patients develop severe autoimmune reactions that involve autoimmune endocrine disorders (type 1 diabetes, thyroiditis), respiratory and nutritive allergy, eczema and severe infections. In different types of allergy (pollen allergy, dust mite, nutritive allergens, contact hypersensitivity, etc.) and autoimmune diseases (such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes) a lower number or decreased functional capability of regulatory T cells have been described. In inflammatory conditions and infections, this cell population has an important task in restricting immune response and protecting the host from excessive damage. This ability of regulatory T cells can be used by some pathogens (Epstein Barr virus, Mycobacterium tuberculosis, Leishmania major, etc.) and tumor cells to avoid host response and therefore contribute to the development of some pathological conditions. The knowledge gained on the phenotype and function of regulatory T cells could be useful in many medical conditions. In allergy, autoimmune diseases and in transplant procedures in medicine it would be desirable to increase their function, thus to partially suppress the immune system activity. On the other hand, in some infections and tumors, it would be preferable to decrease the activity of regulatory T cells and boost the function of effector T cells. Regulatory T cells comprise a very active field of immunology, therefore monitoring and modulating of their activity is of great potential significance in a broad spectrum of clinical conditions. By developing and standardizing methods for their monitoring, it would be possible to follow additional parameters of certain clinical conditions and possibly utilize them in therapy.
调节性T细胞是T细胞的一个亚群,在现代免疫学中已得到广泛研究。它们对于维持外周免疫耐受至关重要,并且在多种临床病症中发挥重要作用,如过敏、自身免疫性疾病、肿瘤、感染以及移植医学领域。基本上,这群细胞对邻近的免疫细胞具有抑制作用,从而有助于局部调节和控制免疫反应。调节性T细胞主要有两类——天然调节性T细胞,它们形成一个独特的细胞谱系,在胸腺中发育,并通过直接的细胞间接触以及分泌的细胞因子发挥调节作用;还有诱导性调节性T细胞,它们在与抗原呈递细胞上呈递的抗原接触后在外周发育,其主要作用方式是通过白细胞介素10(IL-10)和转化生长因子β(TGF-α)细胞因子。天然调节性T细胞在与特定抗原接触后通过T细胞受体被激活,并以抗原非依赖的方式抑制其他T细胞的增殖。调节性T细胞研究中的一个主要困难是缺乏能够识别这些细胞的特异性分子标记。天然调节性T细胞组成性表达表面分子CD25,但许多其他表面和细胞内分子(HLA-DR、CD122、CD45RO、CD62、CTLA-4、GITR、PD-1、Notch、FOXP3等)正在被研究,以进一步明确这些细胞的表型特征。由于调节性T细胞在建立外周免疫耐受中起重要作用,它们的重要性在许多临床病症中都有体现。在IPEX综合征(免疫失调、多内分泌腺病和肠病,X连锁)中,由影响调节性T细胞发育和功能的Foxp3基因突变引起,患者会出现严重的自身免疫反应,包括自身免疫性内分泌疾病(1型糖尿病、甲状腺炎)、呼吸道和营养性过敏、湿疹以及严重感染。在不同类型的过敏(花粉过敏、尘螨、营养性过敏原、接触性超敏反应等)和自身免疫性疾病(如类风湿性关节炎、多发性硬化症和1型糖尿病)中,已发现调节性T细胞数量减少或功能能力下降。在炎症性病症和感染中,这群细胞在限制免疫反应和保护宿主免受过度损伤方面具有重要任务。调节性T细胞的这种能力可被一些病原体(爱泼斯坦-巴尔病毒、结核分枝杆菌、硕大利什曼原虫等)和肿瘤细胞利用,以逃避宿主反应,从而导致一些病理状况的发展。关于调节性T细胞表型和功能的知识在许多医学病症中可能会有所帮助。在过敏、自身免疫性疾病以及医学移植手术中,增加它们的功能从而部分抑制免疫系统活性是可取的。另一方面,在一些感染和肿瘤中,降低调节性T细胞的活性并增强效应性T细胞的功能可能更合适。调节性T细胞构成了免疫学中一个非常活跃的领域,因此监测和调节它们的活性在广泛的临床病症中具有巨大的潜在意义。通过开发和标准化监测它们的方法,有可能追踪某些临床病症的其他参数,并可能将其用于治疗。