Th1/Th2偏移与恶性肿瘤关系的研究进展

辅助性T细胞Th1 /Th2亚群提出以来, 人们对其在机体免疫应答中的作用进行了大量的研究。正常机体的Th1 /Th2型细胞因子处于动态平衡, 当这个平衡失调并向Th1或Th2转化时, 称为Th1 /Th2的偏移。Th1 /Th2的偏移与许多疾病的发生、发展、治疗和转归有密切的关系。Th1 /Th2偏移     

Graves’病患者Th1/Th2免疫应答及性激素对Th1/Th2的影响（文献综述）

Graves’病（GD）是最常见的自身免疫性甲状腺疾病（AITD），其发病机理以体液免疫异常为大家所熟知，但细胞因子在GD中的发病作用越来越受到国内外学者的重视，研究的焦点主要侧重于Th1／Th2细胞平衡紊乱。GD及其他自身免疫性疾病女性显著高发，提示性激素是影响机体免疫功能的重要因素。本文就近年来国内外对GD患者Th1／Th2免疫应答的研究及性激素对Thl／Th2平衡的影响作一综述。     

催乳素与系统性红斑狼疮Th1/Th2型细胞因子分泌异常

系统性红斑狼疮(SLE)是多种因素相互作用引起的自身免疫性疾病,其发病机制复杂。近年来,随着对神经内分泌免疫网络的研究和认识日渐增多加深,发现催乳素(PRL)与多种自身免疫性疾病相关,如SLE、类风湿性关节炎、干燥综合征等,其中与SLE的关系最引人注目,但具体作用机制还未明确。PRL作为一个自分泌/旁分泌的细胞因子,在细胞因子网络中起着重要的作用,影响其他细胞因子的产生。分别从SLE与Th1/Th2型细胞因子分泌异常、PRL与Th1/Th2细胞因子分泌异常、SLE与PRL的关系等作简要的分析非常重要。     

肝移植组织中调节性T淋巴细胞的表达及分布

背景：调节性T细胞在动物肝脏移植免疫耐受诱导中起重要作用。 目的：探讨调节性T细胞在肝移植组织中的表达与分布。 方法：由第一作者检索Medline数据库1990-01/2010-12,万方医学网1990-01/2010-12,中国医院知识仓库1998-01/2010-12文献。英文检索词为“liver transplantation,rejection,immune tolerance,regulatory T cells”;中文检索词为“肝移植,排斥反应,免疫耐受,调节性T淋巴细胞”。 结果与结论：调节性T淋巴细胞是调节机体免疫应答的一类重要调节性细胞,具有辅助体液和细胞免疫的功能,调节性T淋巴细胞及其细胞因子在肝移植免疫中起十分重要的作用：Th1/rh2的平衡与肝移植后免疫反应密切相关,Th1细胞因子分泌增加可致肝移植排斥反应,当Th1/rh2向Th2偏移,易发生免疫耐受反应。临床评价肝移植患者免疫状态需要联合ImmuKnow、T淋巴细胞、血药浓度、肝功能指标检测等相关检查,来有效指导肝移植受体免疫抑制剂的个体化使用。 关键词：调节性T淋巴细胞;免疫耐受;肝移植;排斥反应;综述文献 doi:10.3969/j.issn.1673-8225.2012.05.033     

全氟化合物与儿童哮喘及Th1/Th2免疫应答平衡相关性研究

目的 采用病例对照探讨全氟化合物(PFAAS)暴露与儿童哮喘及Th1型细胞因子白细胞介素(IL)-2,干扰素(IFN)-γ和Th2型细胞因子(IL-4,IL-5)分泌水平的关系.方法 选择231名台北医院就诊的哮喘儿童作为病例组,来自社区的225名自然儿童作为对照组.采用双抗体酶联免疫吸附实验(ELISA)试剂盒检测儿童血清中细胞因子IL-2、IFN-γ、IL-4和IL-10的分泌水平;高效液相色谱仪分析血清中全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)水平.结果 哮喘儿童机体PFOS(33.9μg/L比28.9 μg/L)和PFOA(1.2μg/L比0.5 μg/L)暴露负荷显著的高于对照组儿童,且随着机体PFAAs的增高,儿童患有哮喘的风险呈增高趋势.对哮喘儿童而言,血清PFAAs水平与Th1型细胞因子(IL-2,IFN-γ)存在显著的负相关,而与Th2型细胞因子(IL-4,IL-5)呈正相关关系.结论 PFOS暴露可诱导机体免疫应答平衡紊乱,并向Th2型免疫应答极化.     

Th1和Th2细胞的表面受体及其功能调节

Th细胞根据其所分泌的细胞因子主要分为Th1和Th2两个细胞亚群 ,它们对机体的免疫功能有重要的调节作用。由于Th1和Th2两类细胞显示出完全不同的免疫调节作用 ,研究它们的受体表达不仅有助于对Th1和Th2细胞的功能研究 ,而且对于了解Th细胞向Th1/Th2分化过程有重要意义。本文主要就Th1和Th2细胞的表面受体表达及其功能调节作一综述。     

Th17细胞与肿瘤微环境

Th17细胞是最近发现的一种不同于Thl和Th2的新型CD4+T细胞亚群,以几-23依赖性分泌IL-17,而极少表达IFN-γ和IL-4为特征.Th17细胞具有多种生物学效应,在机体炎性反应、自身免疫性疾病、肿瘤和移植排斥等的发生、发展中发挥重要作用.作为肿瘤免疫治疗的潜在靶点,国、内外对Th17细胞在肿瘤微环境中的调节、分化、诱导的研究尚处于起步阶段.现就Thl7细胞在肿瘤微环境中的生物学效应及其与临床肿瘤关系的最新进展作一综述.     

IL-25和IL-33促进Th2细胞分化的研究进展

Th2细胞介导的免疫应答是机体清除寄生虫感染和变态反应性疾病发生的主要机制.T细胞产生的一些细胞因子能够有效地调节和促进Th2细胞介导的免疫应答.最近的研究发现,肠粘膜上皮细胞分泌的IL-25和IL-33可以诱导几种新型的固有免疫细胞来促进Th2细胞的分化和激活,增加IL-4、IL-5和IL-13的分泌,从而清除体内寄生虫.     

IL-23/Th17轴与自身免疫性疾病

既往研究认为,自身免疫性疾病主要是Th1/Th2平衡失调所致,但就Th1细胞亚群的研究结果并不能完全解释自身免疫性疾病的发病机制.Th17细胞是新发现的CD4+辅助性T细胞亚群,IL-23是Th17细胞赖以存在,并维持其稳态及扩增,促进其分泌IL-17的必需细胞因子.目前认为,越来越多的研究表明,IL-23/Th17轴参与了多种自身免疫性疾病的病理过程.     

Th9细胞与自身免疫性疾病

Th1、Th2、Th17和调节性T细胞（Treg）亚群是CD4＋T细胞亚群中的重要成员,其参与了人类及动物自身免疫性疾病的发病过程.既往认为,IL-9是由CD4＋Th2细胞分泌的细胞因子,是机体免疫应答中重要的调节因子.最近研究表明,机体内可能存在着一群新型的具有分泌IL-9和IL-10能力的CD4＋Th细胞亚群,称之为＂Th9＂细胞.该细胞亚群与自身免疫性疾病的相关性尚不清楚.     

Intravenous IgA complexed with antigen reduces primary antibody response to the antigen and anaphylaxis upon antigen re-exposure by inhibiting Th1 and Th2 activation in mice

Context: Serum IgG, IgE and IgM have been shown to enhance the primary antibody responses upon exposure to the soluble antigens recognized by those antibodies. However, how IgA affects these responses remains unknown.

Objective: We investigated the effects of intravenously administered monoclonal IgA on the immune responses in mice.

Materials and methods: DBA/1J mice were immunized with ovalbumin in the presence or absence of anti-ovalbumin monoclonal IgA. The Th1 and Th2 immune responses to ovalbumin and the anaphylaxis induced by re-exposure to ovalbumin were measured.

Results: IgA complexed with antigen attenuated the primary antibody responses to the antigen in mice, in contrast to IgG2b and IgE. The primary antibody responses, i.e. the de novo synthesis of anti-ovalbumin IgG2a, IgG1 and IgE in the serum, and the subsequent anaphylaxis induced with re-exposure to ovalbumin were reduced by the co-injection of anti-ovalbumin monoclonal IgA at ovalbumin immunization. The Th1, Th2 and Tr1 cytokines interferon-γ, interleukin-4 and interleukin-10, respectively, released from ovalbumin-restimulated cultured splenocytes collected from allergic mice were also reduced by the treatment. The induction of interferon-γ and interleukin-4 secretion by splenocytes from ovalbumin-immunized mice stimulated in vitro with ovalbumin was also significantly reduced by the antigen complexed with anti-ovalbumin IgA.

Conclusion: These data suggest that the direct inhibition of Th1 and Th2 activation by anti-ovalbumin monoclonal IgA participates in the inhibition of the primary antibody responses. IgA plays important immunosuppressive roles under physiological and pathological conditions and is a promising candidate drug for the treatment of immune disorders.     

Altered Immunity in Endometriosis: What Came First?

Background: This study was conducted to summarize current knowledge of the changes within the immune system, from action of macrophages, lymphocytes and NK cells to biological effects of their products. Endometriosis is a complex gynecological disorder defined as a presence of endometrial tissue outside the uterus affecting over 5 million reproductive-aged women in the U.S. alone.

Result: In recent years, the potential role of the immune system in the development of endometriosis has increasingly gained attention. Data summarized in our study showed that the most relevant immunocytes are macrophages residing inside the peritoneal cavity and the ratios of Th1 to Th2 cells. Another crucial immunological parameter is the balance in production of cytokines and chemoatractants.

Conclusions: This review confirms that despite decades of intensive research, the involvement of the immune system remains elusive, as we can recognize the changes, but still do not understand if these changes represent the results of endometriosis or if they are contributing factors. Based on these findings, we also discuss new treatment possibilities.     

六分钟行走试验：运动耐力评价的方法及临床意义

背景：6分钟行走试验是一项便于操作、易于耐受、能较好反映患者日常运动状况的运动耐力试验。近年来6分钟行走试验还用于评价心、肺移植后的功能状态。尤其对于肺移植后原发性移植物无功能患者的运动能力评价具有一定价值。 目的：综述6分钟行走试验在运动耐力评价中的应用及研究进展。 方法：以PubMmed 和中国知网为检索工具,检索关于6分钟行走试验方法及其在胸肺疾病中应用的文章。检索时间范围：1963-01/2010-10,中文关键词为“6分钟行走试验,慢性阻塞性肺疾病”,英文关键词为“6MWT,COPD”。排除重复研究及Meta分析类文献。 结果与结论：从PubMed 和中国知网检索文献40余篇,选择其中23篇作为参考文献。其中论著20篇,指南2篇,述评1篇。结果提示6分钟行走试验对于评价慢性阻塞性肺疾病患者运动耐力和预测预后具有较大的应用价值,且简便易行,重复性好,能客观反映患者的病情状况。     

The Postoperative Immunosuppressive Phenotypes of Peripheral T Helper Cells Are Associated with Poor Prognosis of Breast Cancer Patients

Purpose: T helper cells play essential roles in anti-tumor immune response. However, the postoperative changes of peripheral T cell subsets and their clinical significance in breast cancer patients remain largely unknown.

Methods: We evaluated the perioperative changes of T lymphocyte subsets in invasive breast cancer (IBC) patients and breast fibroadenoma (BF) patients preoperatively (preop) and 6, 24, 72 hours postoperatively (POH6, POH24, and POH72). Proportions of CD3, CD4, CD8, T helper (Th) 1, Th2, Th17 cells, regulatory T cells (Treg), and CD4⁺/CD8⁺, Th1/Th2 ratio were detected by flow cytometry. Changes in T helper cell quantity were correlated to clinicopathological parameters. Furthermore, we explored the association between the perioperative variations of T cell subsets and disease-free survival (DFS) of IBC patients.

Results: In IBC patients, Th1 cells diminished while Tregs elevated in postoperative 72 hours in the peripheral blood. In contrast, no significant perioperative changes of T cell subsets were observed in BF patients. Postoperative lower Th1 cells at POH 72 of IBC patients were correlated with greater tumor burden, HER2 positive and Ki67 positive. The increased Tregs at POH 72 of IBC patients were correlated with larger tumor size and HER2 positive. Th1 cell decline and Treg increment were both associated with shorter DFS in IBC patients.

Conclusions: The variations of peripheral T helper cell subsets showed postoperative immunosuppression and were associated with poor prognosis in IBC patients.     

IL-37 a New IL-1 Family Member Emerges as a Key Suppressor of Asthma Mediated by Mast Cells

In 1986, we reported a multiple biological effect of IL-1 including immunological, inflammatory, and tumor killing activity. Since then other IL-1 family cytokines have been discovered, some with inflammatory and other with anti-inflammatory activity. In this review article, we speculate on the possible inhibitory effect of IL-37 in the light of new findings.

IL-37, formerly termed IL-1 family member 7 (IL-1F7), binding IL-18 receptor α chain, acts as a cytokine with intracellular as well as extracellular functionality and as a natural inhibitor of immune responses and inflammation. IL-37 inhibits many pro-inflammatory cytokine and increases anti-inflammatory cytokines such as IL-10.

Asthma pathogenesis involves multiple cell types including mast cells, which are important cellular constituents of the human innate and adaptive immunity. IL-37 has an impact on inflammatory cytokines generated by mast cells and is beneficial for and protective in asthma. However, the precise mechanism(s), safety, and tolerability of IL-37 are unclear and still remain a mystery.

Abbreviations: GBP (Guanylate Binding Proteins); HMGB1 (High Mobility Group Box protein 1); NLRP (Nucleotide-like Receptor Pyrin domain 1); ASC (Apoptosis-associated Speck-like protein containing CARD, Caspase Recruitment Domain); FGF2 (Fibroblast Growth Factor 2).     

Human monocytes promote Th1 and Th17 responses to Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children. Human immunity to pneumococcal infections has been assumed to depend on anticapsular antibodies. However, recent findings from murine models suggest that alternative mechanisms, dependent on T helper cells, are also involved. Although the immunological events in which T helper cells contribute to acquired immunity have been studied in mice, little is known about how these responses are generated in humans. Therefore, we examined bacterial and host factors involved in the induction of Th1 and Th17 responses, using a coculture model of human monocytes and CD4(+) T cells. We show that monocytes promote effector cytokine production by memory T helper cells, leading to a mixed Th1/Th17 (gamma interferon [IFN-γ]/interleukin-17 [IL-17]) profile. Both T helper cytokines were triggered by purified pneumococcal peptidoglycan; however, the balance between the two immune effector arms depended on bacterial viability. Accordingly, live pneumococci triggered a Th1-biased response via monocyte production of IL-12p40, whereas heat-killed pneumococci triggered a Th17 response through TLR2 signaling. An increased understanding of human T helper responses is essential for the development of novel pneumococcal vaccines designed to elicit cell-mediated immunity.     

Development of DNA array filter useful for the analysis of Th1/Th2 balance]

DNA arrays are useful for determining the expression levels of a number of genes at once. We utilized this technique to evaluate the Th1/Th2 balance in vivo. Immune responses are controlled by two types of helper T cells, Th1 and Th2. Once the balance of Th1/Th2 immunity is disrupted, various immune diseases can develop. Thus, it is important to evaluate the Th1/Th2 balance in each patient for diagnosis, treatment and/or prophylaxis of immune diseases. We have identified a number of genes specifically expressed in Th1 or Th2 cells, and developed a DNA array filter spotted with these genes. We confirmed that this filter is useful for the evaluation of changes in the immune balance in vivo. Clinical application of this technology may lead to the tailor-made therapy of immune diseases through the evaluation of the immune balance in each patient.     

A Positive Feedback Loop Between Th17 Cells and Dendritic Cells in Patients with Endplate Inflammation

Background: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation.

Methods: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined.Results: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells.

Conclusions: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop.     

Innate lymphoid cells: the role in respiratory infections and lung tissue damage

Introduction: Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases.

Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term ‘innate lymphoid cells respiratory viral infections’ in combination with other relevant terms including various respiratory viruses.

Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.