天然调节T 细胞与诱导调节T 细胞的生物学特性

CD4+CD25+FOXP3+的调节T细胞(regulatory T cells,Treg)在维持机体免疫平衡方面起着重要的作用。体外扩增Treg细胞用于治疗自身免疫病、哮喘及诱导器官移植免疫耐受引起人们极大的兴趣。Treg细胞可分为2个亚群,分别为nTreg和iTreg,两者有不同的生物学特性。nTreg在特定条件下,可以分泌具有促进炎症的IL-17;iTreg在体内可丢失FOXP3,失去其免疫抑制功能。Treg细胞用于临床治疗,还有许多问题需要研究解决。     

Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

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Negligible Effect of Sodium Chloride on the Development and Function of TGF-β-Induced CD4+ Foxp3+ Regulatory T Cells

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Preferential control of induced regulatory T cell homeostasis via a Bim/Bcl-2 axis

Apoptosis has an essential role in controlling T cell homeostasis, especially during the contraction phase of an immune response. However, its contribution to the balance between effector and regulatory populations remains unclear. We found that Rag1^−/− hosts repopulated with Bim^−/− conventional CD4⁺ T cells (Tconv) resulted in a larger induced regulatory T cell (iTreg) population than mice given wild-type (WT) Tconv. This appears to be due to an increased survival advantage of iTregs compared with activated Tconv in the absence of Bim. Downregulation of Bcl-2 expression and upregulation of Bim expression were more dramatic in WT iTregs than activated Tconv in the absence of IL-2 in vitro. The iTregs generated following Tconv reconstitution of Rag1^−/− hosts exhibited lower Bcl-2 expression and higher Bim/Bcl-2 ratio than Tconv, which indicates that iTregs were in an apoptosis-prone state in vivo. A significant proportion of the peripheral iTreg pool exhibits low Bcl-2 expression indicating increased sensitivity to apoptosis, which may be a general characteristic of certain Treg subpopulations. In summary, our data suggest that iTregs and Tconv differ in their sensitivity to apoptotic stimuli due to their altered ratio of Bim/Bcl-2 expression. Modulating the apoptosis pathway may provide novel therapeutic approaches to alter the balance between effector T cells and Tregs.     

On the role of retinoic acid in virus induced inflammatory response in cornea

Ocular infection with herpes simplex virus (HSV) can result in a chronic immune inflammatory lesion that is a significant cause of human blindness. A key to controlling stromal keratitis (SK) lesion severity is to identify cellular and molecular events responsible for tissue damage and to counteract them. One potentially useful approach to achieve such therapy is Retinoic Acid (RA). Here we show that RA therapy reduces the severity of SK by having inhibitory effects on the T effector subtypes responsible for orchestrating SK. RA also served to stabilize the function of regulatory T cell (Treg) which counteract inflammatory cell activity. The Treg stabilizing effect was demonstrated by in vitro studies where RA was shown to retain Foxp3 expression when exposed to proinflammatory conditions such as IL-12 and IL-6+TGF-β. in vivo studies revealed that RA exerted its stabilizing effects by downregulating IL-6R expression on Treg after HSV-1 infection and this helped to control the progression of SK. Since the therapy was effective when used both early and after the initiation of lesions, it may represent a valuable means of therapy when used alone or along with additional therapies.     

Focus: Microbiome: Striking a Balance with Help from our Little Friends – How the Gut Microbiota Contributes to Immune Homeostasis

The trillions of microbes that inhabit the human gut (the microbiota) together with the host comprise a complex ecosystem, and like any ecosystem, health relies on stability and balance. Some of the most important members of the human microbiota are those that help maintain this balance via modulation of the host immune system. Gut microbes, through both molecular factors (such as capsular components) and by-products of their metabolism (such as Short Chain Fatty Acids (SCFAs)), can influence both innate and adaptive components of the immune system, in ways that can drive both effector, and regulatory responses. Here we review how commensal microbes can specifically promote a dynamic balance of these immune responses in the mammalian gut.