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1.
Sang-Mo Kwon Jun-Hee Lee Sang-Hun Lee Seok-Yun Jung Da-Yeon Kim Song-Hwa Kang So-Young Yoo Jong-Kyu Hong Ji-Hye Park Jung-Hee Kim Sung-Wook Kim Yeon-Ju Kim Sun-Jin Lee Hwi-Gon Kim Takayuki Asahara 《PloS one》2014,9(8)
Introduction
Despite the crucial role of endothelial progenitor cells (EPCs) in vascular regeneration, the specific interactions between EPCs and hematopoietic cells remain unclear.Methods
In EPC colony forming assays, we first demonstrated that the formation of EPC colonies was drastically increased in the coculture of CD34+ and CD34− cells, and determined the optimal concentrations of CD34+ cells and CD34− cells for spindle-shaped EPC differentiation.Results
Functionally, the coculture of CD34+ and CD34− cells resulted in a significant enhancement of adhesion, tube formation, and migration capacity compared with culture of CD34+ cells alone. Furthermore, blood flow recovery and capillary formation were remarkably increased by the coculture of CD34+ and CD34− cells in a murine hind-limb ischemia model. To elucidate further the role of hematopoietic cells in EPC differentiation, we isolated different populations of hematopoietic cells. T lymphocytes (CD3+) markedly accelerated the early EPC status of CD34+ cells, while macrophages (CD11b+) or megakaryocytes (CD41+) specifically promoted large EPC colonies.Conclusion
Our results suggest that specific populations of hematopoietic cells play a role in the EPC differentiation of CD34+ cells, a finding that may aid in the development of a novel cell therapy strategy to overcome the quantitative and qualitative limitations of EPC therapy. 相似文献2.
Xuebing Feng Dandan Wang Jingjing Chen Lin Lu Bingzhu Hua Xia Li Betty P. Tsao Lingyun Sun 《PloS one》2012,7(12)
Objective
To observe the proportion of peripheral T follicular helper (Tfh) cells in patients with systemic lupus erythematosus (SLE) and to assess the role of steroids on Tfh cells from SLE patients.Methods
Peripheral blood mononuclear cells (PBMCs) from 42 SLE patients and 22 matched healthy subjects were collected to assess proportions of circulating CXCR5+PD1+/CD4+ T cells (Tfh), CD4+CCR6+ T cells (Th17-like) and CD19+CD138+ plasma cells by flow cytometry. 8 of the patients had their blood redrawn within one week after receiving methylprednisolone pulse treatment. Disease activity was evaluated by SLE disease activity index. To test the effect of IL-21 and corticosteroids on Tfh cells in vitro, PBMCs harvested from another 15 SLE patients were cultured with medium, IL-21, or IL-21+ dexamethasone for 24 hours and 72 hours. PBMCs from an independent 23 SLE patients were cultured with different concentrations of dexamethasone for 24 hours.Results
Compared to normal controls, percentages of circulating Tfh cells, but not Th17 cells, were elevated in SLE patients and correlated with disease activity. Proportions of Tfh cells in SLE patients were positively correlated with those of plasma cells and serum levels of antinuclear antibodies. After methylprednisolone pulse treatment, both percentages and absolute numbers of circulating Tfh cells were significantly decreased. In vitro cultures showed an increase of Tfh cell proportion after IL-21 stimulation that was totally abolished by the addition of dexamethasone. Both 0.5 and 1 µM dexamethasone decreased Tfh cells dose dependently (overall p = 0.013).Conclusions
We demonstrated that elevated circulating Tfh cell proportions in SLE patients correlated with their disease activities, and circulating levels of plasma cells and ANA. Corticosteroids treatment down-regulated aberrant circulating Tfh cell proportions both in vivo and in vitro, making Tfh cells a new treatment target for SLE patients. 相似文献3.
Yuan SH Martin J Elia J Flippin J Paramban RI Hefferan MP Vidal JG Mu Y Killian RL Israel MA Emre N Marsala S Marsala M Gage FH Goldstein LS Carson CT 《PloS one》2011,6(3):e17540
Background
Neural induction of human pluripotent stem cells often yields heterogeneous cell populations that can hamper quantitative and comparative analyses. There is a need for improved differentiation and enrichment procedures that generate highly pure populations of neural stem cells (NSC), glia and neurons. One way to address this problem is to identify cell-surface signatures that enable the isolation of these cell types from heterogeneous cell populations by fluorescence activated cell sorting (FACS).Methodology/Principal Findings
We performed an unbiased FACS- and image-based immunophenotyping analysis using 190 antibodies to cell surface markers on naïve human embryonic stem cells (hESC) and cell derivatives from neural differentiation cultures. From this analysis we identified prospective cell surface signatures for the isolation of NSC, glia and neurons. We isolated a population of NSC that was CD184+/CD271−/CD44−/CD24+ from neural induction cultures of hESC and human induced pluripotent stem cells (hiPSC). Sorted NSC could be propagated for many passages and could differentiate to mixed cultures of neurons and glia in vitro and in vivo. A population of neurons that was CD184−/CD44−/CD15LOW/CD24+ and a population of glia that was CD184+/CD44+ were subsequently purified from cultures of differentiating NSC. Purified neurons were viable, expressed mature and subtype-specific neuronal markers, and could fire action potentials. Purified glia were mitotic and could mature to GFAP-expressing astrocytes in vitro and in vivo.Conclusions/Significance
These findings illustrate the utility of immunophenotyping screens for the identification of cell surface signatures of neural cells derived from human pluripotent stem cells. These signatures can be used for isolating highly pure populations of viable NSC, glia and neurons by FACS. The methods described here will enable downstream studies that require consistent and defined neural cell populations. 相似文献4.
Palakkal Jovvian George Rajamanickam Anuradha Nathella Pavan Kumar Vasanthapuram Kumaraswami Thomas B. Nutman Subash Babu 《PLoS neglected tropical diseases》2012,6(10)
Background
Microbial translocation (MT) is the process by which microbes or microbial products translocate from the intestine to the systemic circulation. MT is a common cause of systemic immune activation in HIV infection and is associated with reduced frequencies of CD4+ T cells; no data exist, however, on the role of MT in intestinal helminth infections.Methods
We measured the plasma levels of MT markers, acute-phase proteins, and pro- and anti - inflammatory cytokines in individuals with or without hookworm infections. We also estimated the absolute counts of CD4+ and CD8+ T cells as well as the frequencies of memory T cell and dendritic cell subsets. Finally, we also measured the levels of all of these parameters in a subset of individuals following treatment of hookworm infection.Results
Our data suggest that hookworm infection is characterized by increased levels of markers associated with MT but not acute-phase proteins nor pro-inflammatory cytokines. Hookworm infections were also associated with increased levels of the anti – inflammatory cytokine – IL-10, which was positively correlated with levels of lipopolysaccharide (LPS). In addition, MT was associated with decreased numbers of CD8+ T cells and diminished frequencies of particular dendritic cell subsets. Antihelmintic treatment of hookworm infection resulted in reversal of some of the hematologic and microbiologic alterations.Conclusions
Our data provide compelling evidence for MT in a human intestinal helminth infection and its association with perturbations in the T cell and antigen-presenting cell compartments of the immune system. Our data also reveal that at least one dominant counter-regulatory mechanism i.e. increased IL-10 production might potentially protect against systemic immune activation in hookworm infections. 相似文献5.
Elena G. Kamburova Hans J. P. M. Koenen Martijn W. F. van den Hoogen Marije C. Baas Irma Joosten Luuk B. Hilbrands 《PloS one》2014,9(11)
Background
Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs. Data on their in vivo effects on T- and B-cell phenotype and function are limited.Methods
In a randomized double-blind placebo-controlled study to prevent renal allograft rejection, patients were treated with tacrolimus, mycophenolate mofetil (MMF), steroids, and a single dose of rituximab or placebo during transplant surgery. In a subset of patients, we analyzed the number and phenotype of peripheral T and B cells by multiparameter flow cytometry before transplantation, and at 3, 6, 12, and 24 months after transplantation.Results
In patients treated with tacrolimus/MMF/steroids the proportion of central memory CD4+ and CD8+ T cells was higher at 3 months post-transplant compared to pre-transplant levels. In addition, the ratio between the percentage of central memory CD4+ and CD4+ regulatory T cells was significantly higher up to 24 months post-transplant compared to pre-transplant levels. Interestingly, treatment with tacrolimus/MMF/steroids resulted in a shift toward a more memory-like B-cell phenotype post-transplant. Addition of a single dose of rituximab resulted in a long-lasting B-cell depletion. At 12 months post-transplant, the small fraction of repopulated B cells consisted of a high percentage of transitional B cells. Rituximab treatment had no effect on the T-cell phenotype and function post-transplant.Conclusions
Renal transplant recipients treated with tacrolimus/MMF/steroids show an altered memory T and B-cell compartment post-transplant. Additional B-cell depletion by rituximab leads to a relative increase of transitional and memory-like B cells, without affecting T-cell phenotype and function.Trial Registration
ClinicalTrials.gov NCT00565331相似文献6.
Adrian Egli Moacyr Silva Jr Daire O'Shea Leticia E. Wilson Aliyah Baluch Luiz F. Lisboa Luis G. Hidalgo Deepali Kumar Atul Humar 《PloS one》2012,7(11)
Background
CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation.Methods
We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4+ and CD8+ T-cells, T-regs (CD4+CD25+FoxP3+) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10).Results
Higher initial CMV-specific CD4+ T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4+ T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4+ T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes.Conclusions
This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4+ T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse. 相似文献7.
Sarah Patterson Patricia Moran Elissa Epel Elizabeth Sinclair Margaret E. Kemeny Steven G. Deeks Peter Bacchetti Michael Acree Lorrie Epling Clemens Kirschbaum Frederick M. Hecht 《PloS one》2013,8(7)
Objective
The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.Methods
We studied 128 HIV-infected adults who were not on treatment and had a CD4+ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.Results
Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4+ T cells (r = −0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8+ T cells (r = −0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4+ (r = 0.24, p = 0.018) and CD8+ (r = 0.24, p = 0.017) activation.Conclusions
These data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV. 相似文献8.
Partha Mukhopadhyay Tracy Farrell Gayatri Sharma Timothy R. McGuire Barbara O’Kane J. Graham Sharp 《PloS one》2013,8(11)
Introduction
Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous.Methods
Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis.Results
The proportion of cells expressing CD44highCD24low/neg, side population (SP) cells, ALDH1+, CD49fhigh, CD133high, and CD34high differed, suggesting heterogeneity. Differences in frequency and size of tumor spheres from these populations were observed. Higher rates of proliferation of non-SP, ALDH1+, CD34low, and CD49fhigh suggested properties of transit amplifying cells. Colony formation was higher from ALDH1− and non-SP cells than ALDH1+ and SP cells suggesting a progenitor phenotype. The frequency of clonal colonies that grew in agar varied and was differentially altered by the presence of Matrigel™. In vivo, fewer cells with a stem cell phenotype were needed for tumor formation than “non-stem” cells. Fewer SP cells were needed to form tumors than ALDH1+ cells suggesting further heterogeneities of cells with stem phenotypes. Different levels of cytokines/chemokines were produced by Clone 66 with RANTES being the highest. Whether the heterogeneity reflects soluble factor production remains to be determined.Conclusions
These data demonstrate that Clone 66 murine breast cancer cells that express stem cell phenotypes are heterogeneous and exhibit different functional properties, and this may also be the case for human breast cancer stem cells. 相似文献9.
John E. McKinnon Robbie B. Mailliard Susan Swindells Timothy J. Wilkin LuAnn Borowski Jillian M. Roper Barbara Bastow Mary Kearney Ann Wiegand John W. Mellors Charles R. Rinaldo for the A study team 《PloS one》2014,9(5)
Objectives
Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.Methods
Thirty-four participants with virologic suppression ≥48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD''s 38/69/94/95/158/279).Results
Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92–55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels.Conclusions
Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring.Trial Registration
ClinicalTrials.gov NCT00084019相似文献10.
Melissa R. Nyendak Byung Park Megan D. Null Joy Baseke Gwendolyn Swarbrick Harriet Mayanja-Kizza Mary Nsereko Denise F. Johnson Phineas Gitta Alphonse Okwera Stefan Goldberg Lorna Bozeman John L. Johnson W. Henry Boom Deborah A. Lewinsohn David M. Lewinsohn for the Tuberculosis Research Unit the Tuberculosis Trials Consortium 《PloS one》2013,8(12)
Rationale
Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8+ T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment.Objectives: We sought to determine the relationship of Mtb specific CD4+ T cells and CD8+ T cells with duration of antituberculosis treatment.Materials and Methods
We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4+ and CD8+ T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24.Results
There was a significant difference in the Mtb specific CD8+ T response, but not the CD4+ T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8+ T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4+ T cell during the treatment. The Mtb specific CD4+ T cell response, but not the CD8+ response, was negatively impacted by the body mass index.Conclusions
Our data provide evidence that the Mtb specific CD8+ T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8+ T cell response can detect early treatment failure, relapse, or to predict disease progression. 相似文献11.
Ester Roos-Engstrand Jamshid Pourazar Annelie F Behndig Anders Bucht Anders Blomberg 《Respiratory research》2011,12(1):74
Background
Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.Method
Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.Results
In smokers with normal lung function, the expression of CD25+CD4+ was increased, whereas the proportions of FoxP3+ and CD127+ were unchanged compared to never-smokers. Among CD4+ cells expressing high levels of CD25, the proportion of FoxP3+ cells was decreased and the percentage of CD127+ was increased in smokers with normal lung function. CD4+CD25+ cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.Conclusion
The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25+ helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development. 相似文献12.
Objectives
Several recent lines of evidence indicate that endothelial microparticles are a new biomarker that can be used to monitor endothelial dysfunction in coronary artery disease (CAD). However, data concerning the detection of small microparticles (diameter <0.5 µm) are lacking. The aim of this study was to detect small-size endothelial microparticles (SEMPs) in CAD patients to monitor endothelial dysfunction.Methods
In total, 19 CAD patients and 14 healthy subjects were recruited. The absolute numbers and percentages of CD31+/CD42b− SEMPs and CD62E+ SEMPs were determined by flow cytometry. Clinical parameters were also recorded.Results
The mean percentage of CD62E+ SEMPs was higher in the CAD patient group than in the healthy subject group. The area under the receiver operating characteristic curve of the percentage of CD62E+ SEMPs was 0.795, and the cut-off value was 1.35. There was no correlation between the percentage of CD62E+ SEMPs and various clinical parameters.Conclusion
The percentage of CD62E+ SEMPs is a potential biomarker for monitoring endothelial function in CAD. 相似文献13.
Ga?l Y Rochefort Pascal Vaudin Nicolas Bonnet Jean-Christophe Pages Jorge Domenech Pierre Charbord Véronique Eder 《Respiratory research》2005,6(1):125
Background
Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats.Methods
Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45- CD73+ CD90+ MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure.Results
A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed in vivo bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group.Conclusion
Adhesive BM-derived CD45- CD73+ CD90+ MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions. 相似文献14.
Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum 总被引:1,自引:0,他引:1
Background
Fetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear.Methodology/Principal Findings
We demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the developing cerebellar cortex of naïve rats. We also show that exposure to ethanol during the 3rd trimester-equivalent of human pregnancy reduces CBP levels. CBP is a histone acetyltransferase, a component of the epigenetic mechanism controlling neuronal gene expression. We further demonstrate that the acetylation of both histone H3 and H4 is reduced in the cerebellum of ethanol- treated rats.Conclusions/Significance
These findings indicate that ethanol exposure decreases the expression and function of CBP in the developing cerebellum. This effect of ethanol may be responsible for the motor coordination deficits that characterize fetal alcohol spectrum disorders. 相似文献15.
Corry-Anke Brandsma Machteld N Hylkema Barry WA van der Strate Dirk-Jan Slebos Marjan A Luinge Marie Geerlings Wim Timens Dirkje S Postma Huib AM Kerstjens 《Respiratory research》2008,9(1):17
Background
Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD.The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model.Methods
Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed.Results
Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4+CD25+ T cells and Foxp3 positive cells in the lungs. Additionally, the CD4+CD25+ T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells.Conclusion
These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued. 相似文献16.
Fu-Min Xue Huan-Ping Zhang Hui-Jie Hao Zhao-Yang Shi Chuan Zhou Baisui Feng Ping-Chang Yang 《PloS one》2012,7(12)
Background and Aims
The pathogenesis of inflammatory bowel disease (IBD) has not been fully understood yet. Eosinophils (Eo) are one type of the major proinflammatory cells of the chronic inflammation in the intestine. CD98 is involved in the pathogenesis of a number of inflammations. This study aims to elucidate the role of CD98+ Eos in the initiation of intestinal inflammation.Methods
The colon biopsies were collected from 60 patients with IBD. The expression of CD98 in the biopsies was examined by immunohistochemistry. The serum levels of the flagellin (FGN) antibody and Eo-derived mediators in the culture supernatants were assessed by enzyme-linked immunosorbent assay. The role of FGN on Eo activation was examined in a cell culture model. The role of FGN in the induction of colitis was observed in a mouse model.Results
Compared to normal controls, the frequency of CD98+ Eos was markedly increased in the IBD colon mucosa. FGN were detected in the colon biopsies and in the sera of IBD patients. Exposure to FGN induced the expression of galectin 3 (the ligand of CD98) in dendritic cells. The exposure to galectin 3 activated the CD98+ Eos. After treatment with FGN intrarectally, mice with eosinophilia showed severe inflammation in the colon.Conclusions
The interaction of galectin 3 and CD98 can induce Eos to release chemical mediators that contributes to the initiation of the intestinal inflammation. 相似文献17.
Jessica Nadigel David Préfontaine Carolyn J Baglole Fran?ois Maltais Jean Bourbeau David H Eidelman Qutayba Hamid 《Respiratory research》2011,12(1):149
Background
Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways. We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.Methods
Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects. TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood. CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors. PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.Results
No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects. However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells. Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression. CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ. Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.Conclusions
Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD. CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production. These results provide a new perspective on the role of CD8+ T cells in COPD. 相似文献18.
Background
Recent evidence shows that long non-coding RNA (LncRNA) play important regulatory roles in many biology process, including cell development, activation and oncogenesis. However, the roles of these LncRNAs in the development and activation of CD4+ T cells, which is an important component of immune response, remain unknown.Results
To predict the function of LncRNA in the development and activation of CD4+ T cells, first, we examined the expression profiles of LncRNAs and mRNAs in CD4−CD8− (DN), CD4+CD8+ (DP), CD4+CD8−, and activated CD4+CD8− T cells in a microarray analysis and verified these results by real time PCRs (qPCR). We found that the expression of hundreds of LncRNAs significantly changed in each process of developmental transition, including DN into DP, DP into CD4+CD8−, and CD4+CD8− into activated CD4+ T cells. A Kendall distance analysis suggested that the expression of LncRNAs in DN, DP, CD4+CD8− T cells and activated CD4+ T cells were correlated with the expression of mRNAs in these T cells. The Blat algorithm and GO analysis suggested that LncRNAs may exert important roles in the development and activation of CD4+ T cells. These roles included proliferation, homeostasis, maturation, activation, migration, apoptosis and calcium ion transportation.Conclusion
The present study found that the expression profiles of LncRNAs in different stages of CD4+ T cells are distinguishable. LncRNAs are involved in the key biological process in CD4+ T cell development and activation. 相似文献19.
Mehrnoosh Doroudchi Oleg Yegorov Tom Baumgartner Anne-Elen Kernaleguen Gaelle Breton Michel L. Ndongala Mohamed-Rachid Boulassel Jean-Pierre Routy Nicole F. Bernard Rafick-Pierre Sékaly Bader Yassine-Diab 《PloS one》2012,7(11)
Objective
To determine the function and phenotype of CD8+ T-cells targeting consensus and autologous sequences of entire HIV-1 Nef protein.Methods
Multiparameter flow cytometry-based analysis was used to evaluate the responses of two treatment naïve HIV-infected individuals, during primary and the chronic phases of infection.Results
A greater breadth and magnitude of CD8 IFN-γ responses to autologous compared to clade-B consensus peptides was observed in both subjects. Cross recognition between autologous and consensus peptides decreased in both subjects during progression from primary to chronic infection. The frequencies of TEMRA and TEM CD8+ T-cells targeting autologous peptides were higher than those targeting consensus peptides and were more polyfunctional (IFN-γ+ Gr-B+ CD107a+).Conclusions
Our data indicate superior sensitivity and specificity of autologous peptides. The functional and maturational aspects of “real” versus “cross-recognized” responses were also found to differ, highlighting the importance of a sequence-specific approach towards understanding HIV immune response. 相似文献20.