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CD8+T淋巴细胞与高血压心肌纤维化的研究进展   总被引:2,自引:0,他引:2  
血管生长因子增多,血管平滑肌细胞增殖和炎症在血管重塑方面起到了关键的作用。这种低级的炎症反应导致粘附分子表达,白细胞的侵入,细胞因子的产生,氧化应激的增加,从而激活免疫细胞和血管炎症信号通路,使T淋巴细胞及巨噬细胞等细胞活化,产生和释放多种活性因子,激活心肌的细胞外基质生成细胞,引起胶原形成及代谢异常,并可导致心肌实质细胞的变性、坏死或亚细胞结构变化等,从而引起心肌纤维化一系列病理生理变化。本文主要就CD8+T淋巴细胞在高血压心肌纤维化炎症反应中的细胞毒性作用、诱导细胞凋亡作用、分泌大量的炎症因子、增加MMPs的活性从而影响心肌纤维化的形成等方面做一综述!  相似文献
2.
Diabetic ketoacidosis induces in vivo activation of human T-lymphocytes   总被引:2,自引:0,他引:2  
Diabetic ketoacidosis (DKA) is an inflammatory state associated with immune responses in polymorphonuclear cells (PMN). Activation of subgroup of T-lymphocytes in PMN of DKA patients, however, is not known. We studied in vivo activation of CD4 and CD8 lymphocytes by measuring de novo growth factor receptor for insulin, IGF-1, and IL-2 in eight patients on admission and at resolution of DKA, and compared them with matched controls. The presence of these receptors was demonstrated in all patients' lymphocytes on admission, but not in control subjects. This event was associated with increased levels of thiobarbituric acid-reacting material and dichlorofluorescien, as markers of oxidative stress. Based on these new findings and works in the literature, we hypothesize that hyperglycemia/ketosis results in increased reactive oxygen species, leading to increased levels of cytokines and emergence of growth factor receptors. We propose DKA changes the T-lymphocytes to insulin sensitive tissues as a compensatory mechanism.  相似文献
3.

Background

Adoptive transfer of donor-derived T cells can be applied to improve immune reconstitution in immune-compromised patients after allogeneic stem cell transplantation. The separation of beneficial T cells from potentially harmful T cells can be achieved by using the major histocompatibility complex (MHC) I-Streptamer isolation technology, which has proven its feasibility for the fast and pure isolation of T-cell populations with a single specificity. We have analyzed the feasibility of the simultaneous isolation of multiple antigen-specific T-cell populations in one procedure by combining different MHC I-Streptamers.

Methods

First, the effect of combining different amounts of MHC I-Streptamers used in the isolation procedure on the isolation efficacy of target antigen-specific T cells and on the number of off-target co-isolated contaminating cells was assessed. The feasibility of this approach was demonstrated in large-scale validation procedures targeting both high and low frequent T-cell populations using the Good Manufacturing Practice (GMP)-compliant CliniMACS Plus device.

Results

T-cell products targeting up to 24 different T-cell populations could be isolated in one, simultaneous MHC I-Streptamer procedure, by adjusting the amount of MHC I- Streptamers per target antigen-specific T-cell population. Concurrently, the co-isolation of potentially harmful contaminating T cells remained below our safety limit. This technology allows the reproducible isolation of high and low frequent T-cell populations. However, the expected therapeutic relevance of direct clinical application without in vitro expansion of these low frequent T-cell populations is questionable.

Discussion

This study provides a feasible, fast and safe method for the generation of highly personalized MHC I-Streptamer isolated T-cell products for adoptive immunotherapy.  相似文献
4.
To quantitatively assess the risk of contamination by Pneumocystis depending on the degree of immunosuppression (ID) of the exposed rat hosts, we developed an animal model, where rats went through different doses of dexamethasone. Then, natural and aerial transmission of Pneumocystis carinii occurred during cohousing of the rats undergoing gradual ID levels (receivers) with nude rats developing pneumocystosis (seeders). Following contact between receiver and seeder rats, the P. carinii burden of receiver rats was determined by toluidine blue ortho staining and by qPCR targeting the dhfr monocopy gene of this fungus. In this rat model, the level of circulating CD4+ and CD8+ T lymphocytes remained significantly stable and different for each dose of dexamethasone tested, thus reaching the goal of a new stable and gradual ID rat model. In addition, an inverse relationship between the P. carinii burden and the level of circulating CD4+ or CD8+ T lymphocytes was evidenced. This rat model may be used to study other opportunistic pathogens or even co‐infections in a context of gradual ID.  相似文献
5.
T-lymphocytes (T-cells) are unique in that unlike monocytes, they have no insulin receptors, and are insulin insensitive, but upon activation with antigens develop insulin, IGF-1, and IL-2 receptors, and become insulin sensitive tissues. In vivo activation of these cells has now been demonstrated in patients with diabetic ketoacidosis. We analyzed the genomics and proteomics of activated and non-activated CD4+ and CD8+ T-cells of normal subjects using Affymetrix microarray gene chips and proteomes by SELDI-TOF mass spectrometry analysis. Genes for IL-2, insulin, and IGF-1 receptors were increased at least 2-fold in activated vs non-activated T-cells. Using an expression array containing the entire human genome of 39,500 genes, we evaluated approximately 27,000 genes relevant in physiologic and cellular ontologies. Of these, approximately 10,500 genes were increased in activated cells, compared to about 7,000, which were decreased, and approximately 9500, which were unchanged. Among activated ontologies were signal transduction pathways such as IRS-1, IRS-2, Akt, and glycolytic pathways. To our knowledge this is the first report of an hitherto unreported event. Possible implications of these processes are discussed in the light of their physiological significance.  相似文献
6.
Forty amyotrophic lateral sclerosis (ALS) patients were treated with suppressor factor. The therapy led to the normalization of the immunoregulatory index in approximately two thirds of the patients. The responder patients had a better clinical response, i.e. the degenerative process slowed down or it was even arrested. This favourable effect was accompanied with a significant increase in the patients’ life span. When the therapy had no effect on the CD8 ceils, it was discontinued. Stopping the therapy led to disease progression and death; thus, in some patients, therapy was carried out despite its failure to increase the CD8 cell numbers. Substantial clinical improvement was noticed in these patients. The mean survival of patients with ALS was 2–3 years, whereas ALS patients treated with the suppressor factor survived on the average more than 5 years.  相似文献
7.
Early hematologic changes were studied over a 14 day period in three groups of six rhesus macaques intravenously infected with pathogenic and nonpathogenic isolates of SIVmac. Abnormalities in blood included a mild blood loss anemia, sporadic lymphopenia, and variable CD4+ and CD8 + T lymphocyte numbers. Prominent bone marrow findings in macaques inoculated with pathogenic uncloned SIVmac and molecularly cloned pathogenic SIVmac-239 were hypercellularity, myeloid and megakaryocytic hyperplasia, and lymphoid aggregates. Infrequent mild morphologic abnormalities were present in macaques infected with a nonpathogenic molecular clone, SIVmac-1A11.  相似文献
8.
通过对圈养林麝(Moschusberezovskii)外周血淋巴细胞CD4~+、CD8~+亚群的检测,探讨林麝细胞免疫功能状态,并探索应用流式细胞仪分析其淋巴细胞亚群的方法,为研究林麝重大疾病的病理机制及诊断方法提供科学依据。本研究选取健康林麝和患呼吸道疾病林麝各5头,以双色流式细胞术检测其外周血淋巴细胞CD4~+、CD8~+亚群的含量,并进行比较。结果显示,羊源CD4、CD8的流式荧光抗体能够标记林麝细胞并有效检测;患病林麝与健康林麝相比,外周血CD4~+细胞含量无差异(P 0.05),CD8~+细胞含量则显著降低(P 0.01),CD4~+/CD8~+比值显著增高(P 0.01)。结果表明,患呼吸系统炎性疾病的林麝其外周血淋巴细胞CD8~+亚群变化显著,检测淋巴细胞亚群对林麝疾病的诊断有重要意义。  相似文献
9.
ATP-dependent Lon protease-deficient Salmonella enterica serovar Typhimurium (strain CS2022) appeared to invade successfully the mesenteric lymph nodes (MLN) and Peyer's patches (PP) of BALB/c mice and appeared to be easily eradicated by the host after oral immunization. As detected by flow cytometry, the population of major histocompatibility complex class I (MHC-I)-expressing macrophages and dendritic cells (DCs) was increased in the PP of mice immunized with CS2022 on day 6 after immunization. Thereafter, the population of splenic surface CD69(+) T lymphocytes prepared from mice immunized with CS2022 6 weeks prior to measurement increased as a result of the administration of the extracellular vesicles of RAW264.7 macrophage-like cells derived by Salmonella challenge. In addition, the proliferation of CD8(+) and even of CD4(+)T cells isolated from mouse spleens immunized with CS2022 was enhanced after cocultivation with naive DCs in the presence of the extracellular vesicles. These findings indicate that the extracellular vesicles prepared from the Salmonella-challenged macrophages carried salmonellae antigens to bystander DCs, thereby stimulating T-cell responses. Therefore, as antigen presentation after phagocytosis should be a central process in the T-cell activation that occurs in response to Salmonella infection, an oral immunization with CS2022 sufficiently induces T cell-mediated immunity in mice.  相似文献
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