T细胞与类风湿性关节炎

类风湿性关节炎(RA)是一种慢性、炎症性自身免疫性疾病,发病机制非常复杂,至今尚未阐明.尽管多种免疫细胞和分子被证实参与了RA的关节炎症反应和组织破坏,但抗原特异性T细胞的激活始终被认为是RA发病起始和进展的中心环节.不同亚群T细胞在RA发病中发挥不同作用,以往认为,自身抗原诱导的促炎性Th1细胞活化是RA发病的主要因...     

Th17细胞与Th1细胞在慢性阻塞性肺疾病炎症发病机制中的调控作用

慢性阻塞性肺疾病(COPD)发病的分子机制目前仍不甚清楚,大量证据表明,T淋巴细胞介导的免疫反应贯穿于COPD的各个阶段,导致炎症反应持续放大.近来研究发现,Th1细胞和Th17细胞均参与了COPD的免疫发病过程,通过相互间作用调控COPD的炎症反应.因此,深入了解COPD炎症发病过程中Th17、Th1细胞免疫应答特征、分化及调控功能,对探讨COPD的致病机制以及免疫调节治疗的靶点具有重要意义.     

大肠癌肿瘤微环境中Th17细胞与调节性T细胞的作用及临床意义

大肠癌是全球最常见的恶性肿瘤之一,大肠癌的发生、发展与肠内慢性炎症(CRC)密切相关,而部分炎症细胞及其分泌的细胞因子在这一过程中扮演着重要角色,肿瘤浸润效应T细胞与多种类型肿瘤病人的预后密切相关,辅助性T细胞17(Th17)是新近发现的一类CD4+效应T细胞亚群,在炎症、自身免疫性疾病和肿瘤中发挥积极作用.调节性T细胞(Tregs)在功能上是T细胞的免疫抑制亚群,在自身免疫耐受和抗肿瘤免疫中起重要作用.Th17细胞和Treg细胞之间的动态平衡在保持免疫调控功能中至关重要.     

桥本甲状腺炎免疫相关机制的研究进展

桥本甲状腺炎(HT)是一种器官特异性自身免疫性疾病,发病的具体免疫机制尚未阐明,但相关研究表明HT患者的T细胞和NK细胞数量和功能存在异常。辅助性T细胞和调节性T细胞(Treg)是T细胞的两个重要亚群,前者又包括Th1、Th2、Th17和滤泡辅助性T细胞(Tfh)等细胞。Th1/Th2比例失衡可诱导异常免疫应答;Th17细胞分泌IL-17直接促进甲状腺组织炎性反应损伤甲状腺细胞;Tfh细胞通过分泌IL-21调节B细胞功能,诱导机体特异性抗体的产生;功能异常Treg不能有效抑制自身免疫反应的发生;CD4/CD8比例异常可致免疫功能紊乱;NK细胞的免疫调节异常可影响后续免疫反应的发生。以上免疫机制均发现与HT发生有关,本文将分别对这两类T细胞亚群及NK细胞在HT发病中的作用进行综述。     

Th17细胞和调节性T细胞在炎症性疾病中的研究进展

Th17细胞和调节性T细胞(Treg)是具有相反作用的T细胞亚群,它们的平衡有利于维持机体稳定的免疫状态,在炎症性疾病中发挥重要作用。在炎性条件下,Treg可以转换成Th17细胞,Th17细胞数量增多,Treg数量显著减少或其抑制功能降低,致使Th17细胞/Treg的失衡,从而导致炎症性疾病的发生和发展。Th17细胞/Treg的平衡紊乱已经成为炎症性疾病研究领域中的新热点。本文对Th17细胞和Treg的基本功能作用、两者之间的平衡关系及其机制以及Th17细胞/Treg与炎症性疾病的关系进行了综述,为炎症性疾病的早期诊断、预后及免疫治疗提供新的思路。     

不同类型的调节性T细胞在类风湿关节炎中的作用

类风湿关节炎是一种系统性自身免疫性疾病,以慢性关节炎症、骨和软骨侵蚀以及滑膜组织增生为特征,目前关于RA的发病机制尚未明确。效应性T细胞即辅助性T细胞及其分泌的细胞因子的水平失衡是RA发病的重要机制,其中调节性T细胞作为一类免疫抑制性T细胞,在介导免疫稳态、维持免疫耐受及控制疾病进展方面起重要作用,因此深入研究不同亚型的Treg在RA中的功能和作用可能为RA的治疗提供新思路。     

Th17/Treg细胞平衡在类风湿关节炎发病机制中的研究进展

类风湿关节炎是一种自身免疫性疾病, 具体发病机制不明。辅助性T细胞(helper T cells, Th)17/调节性T细胞(regulatory T cells, Treg)平衡在类风湿关节炎发病中的作用越来越受到重视。Th17细胞及其分泌的细胞因子具有促炎作用, Treg细胞及其分泌的细胞因子具有抑炎作用。Th17细胞增多、Treg细胞减少能够导致关节软骨和骨质的破坏, 引发类风湿关节炎;而调节Th17/Treg细胞平衡能治疗类风湿关节炎。文章就Th17/Treg细胞平衡在类风湿关节炎发病中的作用作一综述。     

Th17：新兴的辅助T细胞

Th17近来逐渐被认为是一个独立的辅助T细胞亚群, 以分泌IL-17主要特征.Th17在防御胞外细菌感染的免疫应答、介导慢性炎症和自身免疫性疾病的发病机制中发挥重要作用.对Th17的进一步深入研究可以加深我们对相关疾病发病机制的认识并指导临床治疗.     

Th17细胞与Treg细胞比例失衡在慢性炎症性疾病中研究进展

慢性炎症性疾病涉及许多疾病的发展过程,如变应性鼻炎、支气管哮喘、类风湿性关节炎（rheumatoid arthritis,R A）、炎症性肠病（inflammator y bowel disease,IBD）等。研究发现,Th17和Treg细胞通过其自身及产生的相应细胞因子,在慢性炎症性疾病发生发展过程中起着重要作用,而Th17和调节性T细胞（T Regulator Cell,Treg细胞）的分化共用了TGF-β这个细胞因子,提示他们在分化过程中有某种关联。本文旨在阐述Th17细胞与Treg细胞比例失衡在相关慢性炎症性疾病的发生发展中所起的关键作用。     

新型免疫抑制因子IL-35研究新进展

IL-35是一种由调节性T细胞(Tr)分泌具有免疫负调作用的新型细胞因子.IL-35通过抑制IL-17等效应分子发挥免疫调节作用,研究表明,Tr、IL-35和Th17参与了自身免疫性疾病,炎症与肿瘤的免疫调节,因此IL-35的上游激活以及下游效应反应机制值得进一步研究探讨.     

CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells

We previously reported that 4C8 monoclonal antibody (mAb) provides a costimulatory signal to human CD4+ T cells and consequently induces regulatory T (Treg) cells, which are hypo-responsive and suppress the polyclonal response of bystander CD4+ cells in a contact-dependent manner. In this study, we identified the antigen of 4C8 mAb as CD52. Costimulation with Campath-1H, a humanized anti-CD52 mAb, also induced Treg cells. Anti-CD52-induced Treg cells suppressed the proliferation of both CD4+ and CD8+ T cells provided with polyclonal or allogeneic stimulation. When Treg cells were induced from Staphylococcal enterotoxin B (SEB) treated cells, they suppressed the response to SEB more efficiently than that to another superantigen, SEA. Furthermore, anti-CD52-induced Treg cells could be expanded by culture with IL-2 followed by CD52-costimulation, and co-injection of expanded Treg cells suppressed lethal xenogeneic graft versus host disease (GvHD) reactions in SCID mice caused by human peripheral blood mononuclear cells (PBMCs).     

Special regulatory T-cell review: Suppressors regulated but unsuppressed

The rise-and-fall and reincarnation of suppressor T cells is reviewed from the perspective of a participant in the field.     

Induction of contact-dependent CD8(+) regulatory T cells through stimulation with staphylococcal and streptococcal superantigens

The bacterial superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes are potent stimulators of polyclonal T-cell proliferation. They are the causes of toxic shock syndrome but also induce CD25⁺ FOXP3⁺ regulatory cells in the CD4 compartment. Several studies have recently described different forms of antigen-induced regulatory CD8⁺ T cells in the context of inflammatory diseases and chronic viral infections. In this paper we show that bacterial superantigens are potent inducers of human regulatory CD8⁺ T cells. We used four prototypic superantigens of S. aureus (toxic shock syndrome toxin-1 and staphylococcal enterotoxin A) and Str. pyogenes (streptococcal pyrogenic exotoxins A and K/L). At concentrations below 1 ng/ml each toxin triggers concentration-dependent T-cell receptor Vβ-specific expression of CD25 and FOXP3 on CD8⁺ T cells. This effect is independent of CD4⁺ T-cell help but requires antigen-presenting cells for maximum effect. The cells also express the activation/regulatory markers cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumour necrosis factor receptor-related protein and skin homing adhesins CD103 and cutaneous lymphocyte-associated antigen. Superantigen-induced CD25⁺ FOXP3⁺ CD8⁺ T cells were as potent as freshly prepared naturally occurring CD4⁺ regulatory T cells in suppressing proliferation of CD4⁺ CD25⁻ T cells in response to anti-CD3 stimulation. Although superantigen-induced CD8⁺ CD25⁺ FOXP3⁺ express interleukin-10 and interferon-γ their suppressive function is cell contact dependent. Our findings indicate that regulatory CD8⁺ T cells may be a feature of acute bacterial infections contributing to immune evasion by the microbe and disease pathogenesis. The presence and magnitude of regulatory CD8⁺ T-cell responses may represent a novel biomarker in such infections. Superantigen-induced regulatory CD8⁺ T cells also have therapeutic potential.     

CD8+ suppressor-mediated regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65

Although potentially autoreactive T cells are present even in healthy subjects, most individuals do not develop autoimmune disease. It has been well demonstrated that CD4+ CD25+ regulatory T cells play a significant role in controlling the expansion of autoreactive T cells in the periphery. However, some healthy individuals exhibit measurable responses to self peptide even in the presence of CD4+ CD25+ regulatory cells. This article describes the regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65 (GAD65), an autoantigen implicated in type-1 diabetes, by autologous CD8+ suppressor T cells. In cells cultured from healthy individuals, the inclusion of autologous CD8+ T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4+ T cell responses to GAD65 peptide. Based on transwell experiments, the observed suppression was cell contact-dependent. However, antibody blocking studies indicated that suppression was mediated by IL-10. Cell fractionation studies suggested that CD8+ suppressor T cells originate from the CD45RA+ CD27- population. The suppression of CD4+ T cell responses to GAD65 in healthy individuals raises the possibility that CD8+ suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population.     

The Tregs' world according to GARP

Naturally occurring CD4⁺CD25^high regulatory T cells (nTreg) are essential for maintaining tolerance. FOXP3 has been established as a molecular marker of nTreg; however, FOXP3 cannot be used as a reliable marker for bona fide human nTreg since effector T cells also up‐regulate FOXP3 expression upon activation. Despite the important function of nTreg, the underlying molecular mechanisms of nTreg‐mediated suppression are far from defined. Previous studies have demonstrated that the TGF‐β latency‐associated peptide (LAP) is expressed on the surface of nTreg, and that immunosuppression can be mediated by membrane TGF‐β; however, it remains unknown how LAP is bound to nTreg and what is the functional significance of its selective expression on activated nTreg. The nTreg's world may now change according to GARP, an orphan toll‐like receptor composed of leucine‐rich repeats. In this issue of the European Journal of Immunology, a study provides further demonstration that GARP is selectively expressed only in activated human nTreg and nTreg cell clones but not in activated effector T cells, confirming GARP as a bona fide nTreg marker. In addition, GARP binds directly to LAP; yet, GARP over‐expression is insufficient to induce modification of latent TGF‐β into active TGF‐β further clarifying its role in nTreg‐mediated suppression.     

Activated T lymphocytes in pre-eclampsia

PROBLEM: The aim of our study was to investigate the activation markets of T CD3(+), T helper CD4(+) and T cytotoxic CD8(+) cells, as well as, the populations of T na?ve CD4(+) CD45RA(+), T memory CD4(+) CD45RO(+) and T regulatory lymphocytes in PE and healthy pregnant women. METHOD OF STUDY: Twenty-five patients with PE and thirty healthy third trimester pregnant women were included in the study. Peripheral blood mononuclear cells were isolated from peripheral blood, stained with monoclonal antibodies and estimated using the flow cytometric method. RESULTS: The percentages of CD4(+)CD25(+), CD4(+)CD25(dim), CD3(+)HLA-DR(+), CD4(+)HLA-DR(+) and CD8(+)HLA-DR(+) cells did not differ between study groups. The population of T regulatory CD4(+)CD25(bright) lymphocytes was significantly lower in the group of patients with PE when compared with the controls (P < 0.01). The percentages of CD3(+)CD25(+) (P < 0.05), CD8(+)CD25(+) (P < 0.05), CD4(+)45RO(+) (P < 0.01) lymphocytes were significantly higher, while CD4(+)CD45RA(+) (P < 0.01) cells--significantly lower in peripheral blood of patients with PE when compared with the control group. CONCLUSION: The increased levels of T CD4(+)45RO(+) and T CD8(+) CD25(+) cells can suggest the activation of CD4(+) and CD8(+) T lymphocytes in pre-eclampsia. It seems possible that the activation of T lymphocytes is associated with the deficiency of T regulatory cells in PE.     

Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses

Natural killer T (NKT) cells constitute a distinct lymphocyte lineage at the interface between innate and adaptive immunity, yet their role in the immune response remains elusive. Whilst NKT cells share features with other conventional T lymphocytes, they are unique in their rapid, concomitant production of T helper type 1 (Th1) and Th2 cytokines upon T-cell receptor (TCR) ligation. In order to characterize the gene expression of NKT cells, we performed comparative microarray analyses of murine resting NKT cells, natural killer (NK) cells and naïve conventional CD4⁺ T helper (Th) and regulatory T cells (Treg). We then compared the gene expression profiles of resting and alpha-galactosylceramide (αGalCer)-activated NKT cells to elucidate the gene expression signature upon activation. We describe here profound differences in gene expression among the various cell types and the identification of a unique NKT cell gene expression profile. In addition to known NKT cell-specific markers, many genes were expressed in NKT cells that had not been attributed to this population before. NKT cells share features not only with Th1 and Th2 cells but also with Th17 cells. Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses.     

CD28 costimulation: Walking the immunological tightrope

CD28 function has typically been associated with the generation of effector T‐cell responses to Ag. However, it is also clear that CD28 plays an important role in Treg‐cell biology. Understanding which functions predominate is important when designing therapeutic interventions based on CD28 targeting. An article by Hünig and colleagues [Eur. J. Immunol. 2013. 43: 188–193] in this issue of the European Journal of Immunology uses an inducible gene deletion approach to reveal that, in the steady state, Treg cells intrinsically require CD28 signals for their maintenance in the periphery, whereas homeostasis of conventional T cells is relatively unaffected. Here we highlight the delicate balance created by the ability of CD28 to modulate both regulatory and effector T‐cell responses.