辅佐细胞在磷酸一乙脂激活γδT细胞中的作用

目的：研究辅佐细胞在非肽类抗原ＭＥＰ激活γδＴ细胞中的作用及机制。方法：用花环沉降法分离出正常人外周血中的Ｔ细胞,通过细胞计数和ＦＡＣＳ,观察ＭＥＰ激活γδＴ细胞时辅佐细胞的作用。结果：ＭＥＰ激活γδＴ细胞需要有ＩＬ－２的持续存在。ＭＥＰ和ＩＬ－２联合作用于Ｔ细胞可少量激活其中的γδＴ细胞,但与ＩＬ－２的单独作用无明显差异。加入辅佐细胞能大大促进ＭＥＰ和ＩＬ－２联合激活γδＴ细胞的作用,且明显强于ＩＬ－２的单独作用。辅佐细胞分泌的上清对ＭＥＰ激活γδＴ细胞无明显促进作用。结论：ＭＥＰ激活γδＴ细胞需要辅佐细胞的参与,可能主要通过与Ｔ细胞间的直接接触而起作用。     

磷酸脂配体体外激活人外周血γδT细胞的研究

人γδT细胞可识别非肽类的磷酸脂分子。本研究用非肽类磷酸脂配体MEP在体外选择性扩增人外周血γδT细胞。MEP激活的PBMC中主要为CD3+ CD45RO+ γδTCR+ 细胞群。激活的γδT细胞可分泌IFN γ ,但不分泌IL 4,因此激活的γδT细胞可能分泌Thl型细胞因子。MEP激活γδT细胞需要有辅佐细胞的存在 ,但不需要抗原的处理和递呈 ,并且激活的γδT细胞对多种肿瘤细胞具有非MHC限制性的细胞毒作用。以上结果提示MEP可有效激活γδT细胞 ,使其表现出独特的免疫学特征和生物学功能。     

γδT细胞在疾病中的作用

γδT细胞是皮肤表皮内淋巴细胞和粘膜组织上皮内淋巴细胞的主要成分之一,为非特异性免疫细胞。活化的γδT细胞具有较强的杀伤活性,具有抗感染、抗肿瘤作用;γδT细胞还可以维持免疫耐受,调节免疫应签,异常可导致自身免疫性疾病的发生。因此尽管γδT细胞在人类庞大复杂的免疫体系中数量较少,但却具有不可替代的重要功能。     

γδT细胞

一小部分T细胞的受体不是由α和β多肽链构成的“常规”T细胞受体(TCRαβ),而是分别由γ和δ链取而代之(TCRγδ)。TCRγδ能够识别抗原。出现在T细胞个体发生的早期。在机体的某些部位,如小鼠的皮肤和肠道TCRγδ占优势,提示γδT细胞可能在抗感染的第一线起着防御作用γδT细胞能分泌淋巴因子,并具有细胞毒活性。由于MHC的非限制性以及CD_4、CD_8两阴性γδT细胞的发现,表明其激活过程可能与已知的αβT细胞不同。结核杆菌抗原能够优先激活γδT细胞,提示γδT细胞可能有一种特异的功能。γδT细胞的数量在许多疾病中稍有增加,但到目前的研究还未能证实γδT细胞有病原性作用。     

γδT细胞的生物学意义

<正>T淋巴细胞表面可分别表达两种与CD3分子相关联的T细胞抗原受体(T cell re-ceptor,TCR):由α链和β链(TCRαβ)或γ链和δ链构成的异质二聚体.人们一直对αβT细胞的结构和功能研究予以很大程度上的关注,而对于γδT细胞研究投入要少些.主要原因可能是人们认为TCRγδ细胞是一个外周淋巴细胞库中的数量较小的亚群,不大可能在免疫应答中起主要作用.γδT细胞约占正常人外周血淋巴细胞总数的3%～10%,在其表面表达CD3分子,但绝大多数不表达CD4及CD8分子.然而在长期进     

γδ+T细胞在抗感染免疫中的作用

γδ+T细胞是一个重要的T细胞亚群,近年研究表明在各种感染性疾病中,γδ+T细胞数明显增加,尤其在消除癌细胞、细菌、病毒、寄生虫等抗感染免疫方面起重要作用,本文就γδ+T细胞在抗感染性疾病研究进展包括γδ+T细胞的组织分布、抗原特性和功能等综述如下.     

PKC在结核杆菌抗原诱导入γδT细胞凋亡中的作用

采用Annexin—V—FITC／PI染色流式细胞术检测细胞凋亡的方法，分别观察Mtb—Ag（10．0μg／ml）刺激特异性激活的人γδT细胞不同时间凋亡情况，并研究Rottlerin（PKC抑制剂）预处理对Mtb-Ag诱导γδT细胞凋亡的影响。结果显示Mtb-Ag刺激3h、6h、12h、24h均可显著诱导γδT细胞凋亡（P〈0．01），凋亡细胞比例在44．21％-51．76％之间；Mtb-Ag诱导γδT细胞凋亡可被Rotflerin（40．0μmol／L）抑制，凋亡抑制率为98．6％。提示PKC途径参与Mtb-Ag激发活化的γδT细胞凋亡过程。     

γδ^＋T细胞在抗感染免疫中的作用

γδ^ T细胞是一个重要的T细胞亚群，近年研究表明在各种感染性疾病中，γδ^ T细胞数明显增加，尤其在消除癌细胞、细菌、病毒、寄生虫等感染免疫方面起重要作用，本文就γδ^ T细胞在抗感染性疾病研究进展包括γδ^ T细胞的组织分布、抗原特性和功能等综述如下。     

γδT细胞在病毒感染中的免疫学作用

γδT细胞属于固有免疫细胞,主要位于皮肤、小肠等黏膜及皮下组织和外周血中。γδT细胞的功能包括抗感染、抗肿瘤、免疫监视、免疫调节和维持免疫耐受等作用。在病毒入侵机体的过程中,γδT细胞表型和功能发生变化,搭建了固有免疫细胞及免疫细胞的桥梁,除了起到直接的细胞毒杀伤作用,还作为免疫调节细胞和抗原递呈细胞发挥了抗感染的免疫功能。     

γδT细胞在免疫应答中的作用概述

γδT细胞作为T细胞的一个特殊亚群，主要分布在粘膜和上皮组织，是机体的一种重要的免疫细胞，主要以MHC非限制性方式识别各娄抗原，如HSP、核苷酸衍生物和磷酸化抗原等，发挥细胞毒作用，并可分泌多种细胞因子如IL-2、IL-3、IL-6、IFN—γ、INF—α等调节免疫应答，在机体抗感染免疫、抗肿瘤免疫、自身免疫疾病等的发生中扮演了重要角色。下面就其在机体免疫应答中的作用作一综述。     

Role of veiled cells in lymphocyte activation

Peripheral blood lymphocytes from normal rabbits or from rabbits hyperimmunized with human immunoglobulin were cultured in 20-μl hanging droplets. The cultures were stimulated with concanavalin A or, in the case of cells from sensitized animals, with human immunoglobulin. The addition to the cultures of small numbers of autologous or allogeneic veiled cells separated from afferent lymph increased the responses to low doses of the stimulants, particularly when the cells were cultured at low cell densities or for short periods of time. At high cell densities or at longer periods of culture, stimulation occurred in the absence of added veiled cells and was associated with clumping of the lymphoid cells and development of cells which morphologically resembled veiled cells found in afferent lymph. The enhanced responses upon addition of small numbers of veiled cells were also correlated with the formation of lymphoid aggregates which were frequently held together by the elongated processes of a single veiled cell. The observations support the view that the veiled cells are lymph-borne precursors of dendritic cells in the lymph nodes. This may provide an in vitro model for the cellular relationships which occur in paracortical cords of lymph nodes following antigenic stimulation.     

Evaluation of accessory cell heterogeneity. III. Role of dendritic cells in the in vitro activation of the antibody response to soluble antigens

Dendritic cells and macrophages obtained from spleen and peritoneal exudate were tested as accessory cells for the activation of lymphokine production by T cells, for supporting T-B cooperation and for the induction of antigen-specific T helper cells. Dendritic cells as well as macrophages were able to activate T cells for interleukin-2 secretion and functioned as accessory cells in T-B cooperation, but only macrophages induced T helper cells, which cooperate with B cells by a linked recognition interaction, to soluble antigens. Dendritic cell- and antigen-activated T cells also did not help B cells in the presence of Con A supernatants which contained various T cell- and B cell-stimulatory factors. The failure of dendritic cells to differentiate memory into functional T helper cells, but their efficient accessory cell function in T-B cooperation, where functional T helper cells are already present, can be best explained by a differential accessory cell requirement for T helper cell activation dependent on the differentiation stage of the T helper cell.     

The role of accessory cells in polyclonal T cell activation. III. No requirement for recognition of H-2-encoded antigens on accessory cells

Highly purified murine lymph node T cells were used to test the hypothesis that polyclonal T cell activation requires the recognition of mitogen-modified major histocompatibility complex (MHC) antigens on accessory cells (AC) by the T cells. A variety of tumor cells lines, including macrophage, B and mast cell tumors, as well as thymomas, were shown to function as AC in concanavalin A-induced T cell activation, even if they expressed only one class of MHC antigens or none at all. In contrast to antigen-specific responses, where the Lyt-2+ phenotype is reportedly associated with recognition of class I MHC antigens, T cells enriched for or depleted of Lyt-2+ cells were not preferentially activated in the presence of class I- or class II-positive AC, respectively. In addition, as shown by others in the guinea pig and in the rat systems, T cell proliferation induced by oxidation of cell surface sugars is equally effective if T cells or AC are oxidized. T cell mitogens, therefore, do not seem to act by altering MHC antigens on AC, but rather by providing T cell-AC contact via their agglutinating properties.     

Roles of multiple accessory molecules in T-cell activation

Accessory molecules expressed on T cells can mediate adhesion between T cells and other cells, or the extracellular matrix. The same T-cell accessory molecules participate in a dialogue with their ligands (counter-receptors) on the antigen-presenting cells, and elicit signals that determine the specifics of activation and subsequent differentiation of the T cells and antigen-presenting cells.     

Cytokines amplify the function of accessory cells

Accessory cells have two broad functions at the onset of T cell-mediated immunity. One is the "presentation" of antigen in association with MHC products. The other is a "sensitization" function which is thought to require IL-1 and leads to the development of lymphoblasts that secrete lymphokines and respond to T cell growth factors. This review summarizes evidence, much of it recent, that specific cytokines upregulate both the presentation and sensitization functions of accessory cells. Lymphokines, particularly IFN-gamma, upregulate class II MHC products on macrophages and many non-leukocytes, but not dendritic cells. The enhanced levels of class II improve presentation to T lymphoblasts, but not the sensitization of unprimed and memory T cells. Dendritic cells in lymph and lymphoid organs are active accessory cells for primary responses without any supplementation by exogenous cytokines. IL-1, while not a product of dendritic cells, further amplifies their function several fold. In thymus, IL-1 has a second effect, including the formation of Ia+ thymic dendritic cells from Ia- precursors. Granulocyte-macrophage colony stimulating factor (GM-CSF) is an important cytokine for epidermal Langerhans cells, which are immature dendritic cells. GM-CSF maintains viability in culture, and enhances the sensitization function for primary responses 10-20 fold. Why does the immune system regulate expression of Ia on many cell types, as well as dendritic cell function? In the discussion, it is proposed that the local modification of accessory cells by cytokines helps to reduce anti-self or autoreactive T cell responses, and to enhance the retention of sensitized T cells at sites of antigen deposition.     

Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells.

Previous studies by our lab and others established that co-crosslinking sIg and IgG receptor FcgammaRIIb in B cells in a feedback suppression model (negative signaling) promoted tyrosine phosphorylation of the inositol 5-phosphatase SHIP and its interaction with Shc and that these events were associated with inhibition of the Ras pathway. We therefore hypothesized a competition model in which the SH2 domain of SHIP competes with that of Grb2 for binding to phospho-Shc to inhibit the Ras pathway. Here, we provide evidence consistent with this hypothesis. First, FcgammaRIIb-deficient B cells, which do not undergo SHIP tyrosine phosphorylation nor interaction with Shc, displayed an active Ras pathway under negative signaling conditions; reconstitution of FcgammaRIIb expression restored the block in Ras. Second, under conditions of negative signaling leading to SHIP-Shc interaction in wild-type B cells, we observed a profound reduction in the activation-induced association of Grb2 to Sos. Experiments reported here and elsewhere revealed the Grb2-Sos interaction required the engagement of the Grb2 SH2 domain by phospho-Shc. Third, we demonstrated that phospho-Shc cannot concomitantly bind Grb2 and SHIP, indicating that the two proteins competed for the same phospho-tyrosine residue on Shc. These data are consistent with the proposed competition model, and further indicate that the activation induced Grb2-Sos association is rate limiting for Ras activation.