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1.
丙型肝炎患者外周血单核细胞中丙型肝炎病毒复制的研究 总被引:2,自引:0,他引:2
9例临床诊断为丙型肝炎患者,研究其外周血单核细胞中HCVRNA的存在及复制。9例患者血清标本抗-HCV及HCVRNA均为阳性,采用高敏感的逆转录一套式PCR法测定其外周血单核细胞中HCV正、负链RNA,结果9例患者外周血单核细胞中7例HCV正链RNA阳性,3例HCV负链RNA阳性,证实部分丙肝患者外周血单核细胞中存在HCV的复制,表明肝细胞并非为HCV感染与复制的唯一场所。 相似文献
2.
目的 研究慢性乙型肝炎患者PBMC和活检肝组织的APOBEC3G(A3G)mRNA表达状况并探讨两者之间的相关性;研究A3G mRNA转录表达水平与血清HBV DNA、ALT、PT水平及乙型肝炎肝组织学活动度Knodell计分的相关性.方法 采用实时荧光相对定苗RT-PCR的方法 检测45例慢性乙型肝炎患者PBMC及肝组织中A3G mRNA的表达水平,同时采用实时荧光定量PCR方法 检测血清HBV DNA;常规检测TBil、ALT、PT及乙型肝炎肝组织学活动度Knodell计分.同时设15例健康体检者为阴性对照组.结果 ①慢性乙型肝炎患者PBMC、肝组织均表达A3G mRNA.PBMC A3G mRNA表达水平与活检肝组织A3G mRNA表达呈正相关(r=0.457,P<0.05);②PBMC A3G mRNA与肝组织炎症活动度呈负相关(r=-0.441,P<0.05);③PBMC A3G表达水平与HBV DNA呈正相关(r=0.299,P<0.05),与TBil、ALT、PT无相关性.结论 本组研究显示:①体内研究慢性乙型肝炎患者A3G mRNA抗HBV作用,可首选外周血作为临床适用样本.②慢性乙型肝炎患者PBMC A3G mRNA水平可预测其肝组织损害程度,PBMC A3G mRNA水平越高,肝组织损害越轻. 相似文献
3.
4.
Gaëlle Dzangué-Tchoupou Kuberaka Mariampillai Loïs Bolko Damien Amelin Wladimir Mauhin Aurélien Corneau Catherine Blanc Yves Allenbach Olivier Benveniste 《Autoimmunity reviews》2019,18(4):325-333
Background
Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.Objectives
Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.Methods
Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).Results
Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.Conclusion
Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease. 相似文献5.
Takahashi HK Morichika T Iwagaki H Tamura R Kubo S Yoshino T Mori S Akagi T Tanaka N Nishibori M 《Clinical immunology (Orlando, Fla.)》2003,108(3):274-281
Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine. 相似文献
6.
Afzelius P Nielsen JO 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2000,108(1):74-78
HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro. Sumatriptan, a 5HT1d receptor agonist, inhibits the activity of adenylyl cyclases, the enzymes responsible for regulation of the intracellular levels of cAMP. In a preliminary study sumatriptan increased the proliferative responses of PBMC to a polyclonal activator in vitro in 9 of 10 HIV-seropositive individuals (p=0.007), and in 7 of 9 healthy blood donors (p=0.05). This was probably due to a decrease in the intracellular level of cyclic AMP. 相似文献
7.
Isolation and subfractionation of human peripheral blood mononuclear cells (PBMC) by density gradient centrifugation on Percoll 总被引:7,自引:0,他引:7
The use of Percoll for isolation and subfractionation of PBMC and T-lymphocytes by discontinuous and continuous density gradient centrifugation is described: PBMC were isolated from human peripheral blood by discontinuous density gradient centrifugation on Percoll. The use of Percoll instead of Ficoll-Isopaque has the advantage that Percoll, in contrast to Ficoll-Isopaque, does not alter the density of monocytes. Therefore, a better separation of lymphocytes and monocytes was achieved after subsequent continuous density gradient centrifugation on Percoll. E-RFC were isolated by discontinuous density gradient centrifugation after a first low speed centrifugation step banding lymphocytes and SRBC on a Percoll-Ficoll cushion, and a subsequent high speed centrifugation step separating high density rosettes and SRBC from low density non-E-RFC. The advantage of this procedure is the short time of performance and that there is no need to resuspend the lymphocyte/SRBC pellet. PBMC, nph.PBMC T-lymphocytes were further subfractionated by continuous density gradient centrifugation on Percoll. The method described here resulted in a good separation of lymphocytes and monocytes. However, to obtain lymphocyte fractions with minute numbers of contaminating monocytes, a depletion of monocytes prior to further subfractionation of the lymphocytes by continuous density gradient centrifugation is recommended. A marker analysis of T-lymphocytes subfractionated by continuous density gradient centrifugation on Percoll shows that high density T-lymphocytes are enriched in ANAE positive lymphocytes of type 1 and depleted of ANAE positive lymphocytes of type 2. Low density T-lymphocytes are enriched in ANAE type 2 cells and depleted of ANAE type 1 cells. On the other hand, no considerable differences were found when analyzing the T-cells from different fractions for differentiation antigens by means of monoclonal antibodies (anti Lyt 3, OKT4, and OKT8). The results may indicate that subfractionation of T-lymphocytes by continuous density gradient centrifugation on Percoll provided T-cells in different functional states rather than T-cells of distinct subclasses. 相似文献
8.
9.
Peripheral blood mononuclear cell proliferative responses in the first year of life in babies born to allergic parents 总被引:4,自引:0,他引:4
E. A. MILES J. A. WARNER A. C. JONES B. M. COLWEEL T. N. BRYANT J. O. Warner 《Clinical and experimental allergy》1996,26(7):780-788
Background Raised peripheral blood mononuclear cells (PBMCs) proliferative responses to food allergens have been demonstrated in children with established atopic dermatitis. Objective In this report we investigate the PBMC proliferative responses to inhalant and food allergens from babies at birth, 6 months and 1 year of age, born to atopic and non-atopic parents. Methods PBMCs, separated by density gradient centrifugation. were cultured for 6 days with autologous plasma and a range of allergens (house dust mite [HDM], cat, grass pollen, tree pollen, betalactoglobulin and ovalbumin). Proliferative responses were measured by the uptake of [3H] thymidine added for the final 18 h of culture. Results At birth, infants born to atopic parents who developed allergic disease by 1 year of age had significantly more positive responses (stimulation index ± 2 with a value of ± 1000 cpm above background) to HDM (P = 0.0091), betalactoglobulin (P= 0.0166) and ovalbumin (P = 0.0035) than newborns who did not develop allergy. Tnfants who developed allergy also had significantly more positive responses to HDM (P - 0.03) and ovalbumin (P = 0.0057) than babies, born to non-atopic parents, who did not develop allergies. At 6 months of age a significant fall in response to HDM (P = 0.003) and cat fur extract (P = 0.006) was seen in infants who developed allergic disease by 1 year of age. A similar pattern was seen for proliferative responses to betalactoglobulin and ovalbumin (P = 0.0006. P= 0.004). Conversely, proliferations to grass and tree pollen extracts increased at 6 months (P = 0.04. P = NS) and 1 year (P= NS. P= 0.01) compared with birth which was significant for infants who did not develop allergic disease. Conclusion Proliferative responses to seasonal allergens increased over the first year of life whilst those to perennial allergens, both inhalant and food, fell. This suggests either the induction of a systemic immune tolerance by perennial exposure to antigens or movement of sensitized cells to target organs where allergen exposure occurs. This process may be independent of the development allergic disease. 相似文献
10.
Irina Lehmann Carmen Rder-Stolinski Karen Nieber Gundula Fischder 《Experimental and toxicologic pathology》2008,60(2-3):185-193
An in vitro cell culture system based on an air/liquid culture technique was developed which allows a direct exposure of cells to volatile chemicals without medium coverage. For the establishment of the experimental system, chlorobenzene was used as a model compound. Chlorobenzene is a volatile organic compound which is mainly used as a solvent. Beside other adverse health effects, chlorobenzene exposure has been shown to be associated with respiratory tract irritations, Th2 differentiation, and allergic sensitizations. Human peripheral blood mononuclear cells (PBMC) and lung epithelial cells (A549) were exposed to chlorobenzene via gas phase for 20 h. Additionally, PBMC were incubated with culture supernatants from exposed lung epithelial cells. High chlorobenzene concentrations (100 g/m(3)) induced IL-8 production in A549 cells, whereby lower concentrations (10 microg/m(3)-1 g/m(3)) stimulated the secretion of the monocyte chemoattractant protein-1 (MCP-1). A direct effect of chlorobenzene on the cytokine secretion of PBMC was not found. However, if PBMC were incubated with culture supernatants of exposed lung cells, an enhanced production of the Th2 cytokine IL-13 was observed. This induction was prevented in the presence of an anti-MCP-1 antibody. Our data suggest that chlorobenzene induces the production of inflammatory mediators in lung cells. The primary chlorobenzene caused release of MCP-1 in lung epithelial cells may secondarily result in a Th2 differentiation in T lymphocytes. These findings may contribute to the understanding of how chlorobenzene mediates the development of inflammatory reactions in the airways and contributes to the development of an allergic reactivity. 相似文献