CD8α+树突状细胞研究进展

根据细胞表面CD8α的表达差异,小鼠脾脏中树突状细胞(DC)可以分为2种,即CD8α-DC和CD8α+ DC,二者功能迥异.本文回顾了近年来CD8α+ DC的研究动向,重点分析了CD8α+ DC的在肿瘤免疫、移植免疫和生殖免疫等中的作用.     

Is there a balance between microglia and astrocytes in regulating Th1/Th2-cell responses and neuropathologies?

The brain is often considered an immunologically privileged organ. However, evidence that both microglia and astrocytes secrete cytokines has led to the proposal that there is a balance between these cells in regulating local immune reactions, including Th1/Th2 responses.     

CD3/CD8设门在FCM检测Th1/Th2亚型中的应用

目的　探讨流式细胞术准确、灵敏检测Th1/Th2细胞的新方法。方法　采用荧光mAbCD3和CD8设门 ,准确找到CD4 + T细胞群 ,然后进行Th1/Th2细胞分析 ,并与单用CD4设门进行比较。结果　以CD3/CD8设门较单用CD4设门 ,对靶细胞的定位较为准确 ,测量所获图形美观、清楚并有规律。结论　以CD3/CD8设门 ,可提高检测Th1/Th2细胞的准确性 ,同时也可应用于Tc1/Tc2细胞的检测分析 ,是检测基础和临床免疫样品较理想的方法     

CD8α⁺β⁻ and CD8α⁺β⁺ plasmacytoid dendritic cells induce Foxp3⁺ regulatory T cells and prevent the induction of airway hyper-reactivity

Dendritic cells (DCs) control the balance between protection against pathogens and tolerance to innocuous or self-antigens. Here, we demonstrate for the first time that mouse plasmacytoid DCs (pDCs) can be segregated into three distinct populations, exhibiting phenotypic and functional differences, according to their surface expression of CD8α or CD8β as CD8α⁻β⁻, CD8α⁺β⁻, or CD8α⁺β⁺. In a mouse model of lung inflammation, adoptive transfer of CD8α⁺β⁻ or CD8α⁺β⁺ pDCs prevents the development of airway hyper-reactivity. The tolerogenic features of these subsets are associated with increased production of retinoic acid, which leads to the enhanced induction of Foxp3⁺ regulatory T cells compared with CD8α⁻β⁻ pDCs. Our data thus identify subsets of pDCs with potent tolerogenic functions that may contribute to the maintenance of tolerance in mucosal sites such as the lungs.     

Splenic CD8α⁺ dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8⁺ T-cell memory

Memory CD8⁺ T lymphocytes are critical effector cells of the adaptive immune system mediating long‐lived pathogen‐specific protective immunity. Three signals – antigen, costimulation and inflammation – orchestrate optimal CD8⁺ T‐cell priming and differentiation into effector and memory cells and shape T‐cell functional fate and ability to protect against challenge infections. While among the conventional spleen DCs (cDCs), the CD8α⁺ but not the CD8α^? cDCs most efficiently mediate CD8⁺ T‐cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I‐associated antigens, is most efficient at inducing naïve CD8⁺ T‐cell differentiation into pathogen‐specific protective memory cells in vivo. Moreover, the origin of the required signals is still unclear. Using mice infected with the intracellular bacterium Listeria monocytogenes, we show that splenic CD8α⁺ cDCs become endowed with all functional features to optimally prime protective memory CD8⁺ T cells in vivo within only a few hours post‐immunization. Such programming requires both cytosolic signals resulting from bacterial invasion of the host cells and extracellular inflammatory mediators. Thus, these data designate these cells as the best candidates to facilitate the development of cell‐based vaccine therapy.     

可溶性CD8α链基因克隆及序列分析

可溶性 CD8抗原(sCD8)是从 CD8~ 细胞分泌或脱落至细胞外的白细胞分化抗原,sCD8与免疫调控和再生障碍性贫血等疾病有着密切关系。为从膜 CD8抗原基因中获得具有编码可溶性 CD8分子的基因,我们以 CD8抗原复合体分子的主要亚基α链基因为改构对象,采用逆转录重组 PCR 方法,在基因扩增的同时进行 DNA 重组拼接,除去编码 CD8α链穿膜序列的 DNA,从而克隆出 sCD8α链基因,并对重组的sCD8α链基因进行了序列分析.sCD8α链基因的克隆为进一步研究其表达及可溶性 CD8抗原在免疫调控中的功能奠定了基础.     

头孢地嗪增加老年细菌性肺炎患者外周血CD4/CD8和Th1/Th2细胞比例

目的探讨头孢地嗪对老年细菌性肺炎患者外周血T淋巴细胞CD4/CD8和Th1/Th2细胞比例的影响。方法选取老年细菌性肺炎患者63例,以随机数字表分为两组;对照组31例采用头孢三嗪静脉滴注疗法,观察组32例采用头孢地嗪静脉滴注疗法治疗。分别于治疗前后抽取患者空腹静脉血,以流式细胞仪测定CD4/CD8和Th1/Th2的细胞计数比;以ELISA试剂盒测定Th1细胞分泌因子白细胞介素2(IL-2)、γ干扰素(IFN-γ)与Th2细胞分泌因子IL-4、IL-10的血清浓度。结果治疗前,两组患者的各项指标均无明显差异。治疗后,观察组患者CD4+细胞、Th1细胞比例增加,Th2细胞比例降低,CD4/CD8和Th1/Th2比值均显著高于对照组;同时,观察组患者血清IL-2、IFN-γ浓度显著高于对照组,IL-4、IL-10浓度显著低于对照组。结论头孢地嗪能够提高老年细菌性肺炎患者细胞免疫功能,纠正外周血T淋巴细胞CD4/CD8和Th1/Th2比例失调。     

CD8α^＋ DC的系谱源性

树突状细胞(DC)是来源于骨髓造血干细胞的一组具有异质性的细胞群体。它们的系谱来源一般分为两大类，即髓系来源和淋巴系来源。在以往的研究中，根据鼠体内的DC是否有CD8α的表达而将其分为CD8α^ DC和CD8α^ DC，并认为它们分别代表骨髓系源性和淋巴系源性。然而，最新的实验却证明CD8α的是否表达并不反映DC的个体发生而是反映了DC的成熟状态。本文将就此观点对近来的相关研究作一综述。     

CD8α~+DC的系谱源性

树突状细胞 (DC)是来源于骨髓造血干细胞的一组具有异质性的细胞群体。它们的系谱来源一般分为两大类 ,即髓系来源和淋巴系来源。在以往的研究中 ,根据鼠体内的DC是否有CD8α的表达而将其分为CD8α-DC和CD8α+ DC ,并认为它们分别代表骨髓系源性和淋巴系源性。然而 ,最新的实验却证明CD8α的是否表达并不反映DC的个体发生而是反映了DC的成熟状态。本文将就此观点对近来的相关研究作一综述。     

096 CD8α+DC的系谱源性

树突状细胞(DC)是来源于骨髓造血干细胞的一组具有异质性的细胞群体.它们的系谱来源一般分为两大类,即髓系来源和淋巴系来源.在以往的研究中,根据鼠体内的DC是否有CD8α的表达而将其分为CD8α-DC和CD8α+DC,并认为它们分别代表骨髓系源性和淋巴系源性.然而,最新的实验却证明CD8α的是否表达并不反映DC的个体发生而是反映了DC的成熟状态.本文将就此观点对近来的相关研究作一综述.     

CD8： Adhesion Molecule, Co-Receptor and Immuno-Modulator

CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes, which are important components in cellular immunity, esp. in the immune response to cancer and chronic infections. There are two forms of CD8, either as an alphaalpha homodimer or alphabeta heterodimer. It acts as an "assistant" or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor (alphabeta TCR) and its ligand peptide major histocompatibility complex (pMHC). CD8 also binds to pMHC but away from the interface of pMHC and TCR contact, thereof no influence on the specificity of this interaction. If the TCR and CD8 bind to the same pMHC at the same time, CD8 is defined as a co-receptor, functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway; if CD8 binds to pMHC independently of the TCR, it is defined as an adhesion molecule. At present, the co-receptor function theory is dominated in the field. Recent study has also shown that murine CD8 alphaalpha binds to TL antigen, an MHC homologue, therefore acts as an immuno-modulator. In this review, we discuss these current understandings of the three aspects of the CD8 functions and their structural basis.     

Generation and Regulation of CD8＋ Regulatory T Cells

Research into the suppressive activity of CD4＋FoxP3＋ T regulatory cells （Treg） has defined a sublineage of CD4＋ cells that contribute to self-tolerance and resistance to autoimmune disease. Much less attention has been given to the potential contribution of regulatory sublineages of CD8＋ cells. Analysis of a small fraction of CD8＋ cells that target autoreactive CD4＋ cells through recognition of the MHC class Ib molecule Qa-1 in mouse and HLA-E in human has revitalized interest in CD8＋ Treg. Here we summarize recent progress and future directions of research into the role of this CD8＋ sublineage in resistance to autoimmune disease. Cellular ＆ Molecular Immunology. 2008; 5（6）：401-406.     

CD4:CD8 ratio and HIV infection: the ‘tap-and-drain’ hypothesis

The balance of CD4⁺ and CD8⁺ T cells in humans is controlled by a major autosomal gene. Here, Alberto Amadori and colleagues propose that in view of the high CD4⁺ cell turnover during HIV infection, individuals genetically predisposed to a high CD4:CD8 ratio can withstand HIV-associated CD4⁺ cell losses better than those predisposed to a low ratio.     

GM-CSF increases cross-presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

Resident CD8(+) DCs perform several functions, including cross-presenting antigen and rapidly engulfing the Gram-positive intracellular pathogen Listeria monocytogenes. Little is known about how these functions of CD8(+) DCs are modulated. Here, we show that granulocyte-macrophage CSF (GM-CSF), a cytokine that exists at low levels at steady state but is elevated during infection and inflammation, enhances cross-presentation and rapid uptake of L. monocytogenes by resident CD8(+) DCs. This previously unrecognized functional enhancement of CD8(+) DCs by GM-CSF was independent of promoting DC survival in vitro. Enhancement of these functions by GM-CSF was also marked by CD103 expression on CD8(+) DCs that was strongly regulated by GM-CSF. Our findings not only identify GM-CSF as a key molecule regulating CD8(+) DC function, but also as a factor responsible for functional heterogeneity of CD8(+) DCs that is at least substantially demarcated by CD103 expression.     

CD2 and CD8α define porcine γδ T cells with distinct cytokine production profiles

γδ T cells are a remarkably prominent T-cell subset in swine with a high prevalence in blood. Phenotypic analyses in this study showed that CD2⁻ γδ T cells in their vast majority had a CD8α⁻SLA-DR⁻CD27⁺ phenotype. CD2⁺ γδ T cells dominated in spleen and lymph nodes and had a more heterogeneous phenotype. CD8α⁺SLA-DR⁻CD27⁺ γδ T cells prevailed in blood, spleen and lymph nodes whereas in liver a CD8α⁺SLA-DR⁺CD27⁻ phenotype dominated, indicating an enrichment of terminally differentiated γδ T cells. γδ T cells were also investigated for their potential to produce IFN-γ, TNF-α and IL-17A. Within CD2⁺ γδ T cells, IFN-γ and TNF-α single-producers as well as IFN-γ/TNF-α double-producers dominated, which had a CD8α⁺CD27^+/− phenotype. IL-17A-producing γδ T cells were only found within CD2⁻ γδ T cells, mostly co-produced TNF-α and had a rare CD8α⁺CD27⁻ phenotype. However, quantitatively TNF-α single-producers strongly dominated within CD2⁻ γδ T cells. In summary, our data identify CD2 and CD8α as important molecules correlating with functional differentiation.