Level of CD14<Superscript>+</Superscript>-endothelial progenitor cells is not associated with coronary artery disease or cardiovascular risk factors

There is evidence for two subpopulations among circulating endothelial progenitor cells (EPCs), i.e., CD34⁺-EPCs and CD14⁺-EPCs. Prior studies on the relationship between the level of EPCs and coronary artery disease (CAD), either did not distinguish between the two types of EPCs or studied only CD34⁺-EPCs. We therefore investigated whether the number of circulating CD14⁺-EPCs correlates with either CAD and/or cardiovascular risk factors. Circulating CD14⁺-EPCs—as defined by the surface markers CD14⁺KDR⁺—were analyzed by flow cytometry in 100 individuals [34 control subjects, 41 patients with stable CAD and 25 patients with acute coronary syndromes (ACS)]. The level of circulating CD14⁺-EPCs was not significantly different in patients with normal coronary arteries compared to those with stable CAD or ACS. Neither was there any association between the severity of CAD or risk factors and the number of circulating CD14⁺-EPCs. Thus, the number of circulating CD14⁺-EPCs was not significantly correlated either with the severity of coronary disease or with cardiovascular risk factors.     

CD31+ T cells represent a functionally distinct vascular T cell phenotype

In contrast to CD3⁺/CD31^? cells, CD3⁺/CD31⁺ cells aid in endothelial repair and revascularization. There are limited data regarding the functional differences between circulating CD3⁺/CD31⁺ and CD3⁺/CD31^? cells that may contribute to their divergent cardiovascular effects. The aim of the present study was to characterize functional differences between CD3⁺/CD31⁺ and CD3⁺/CD31^? cells. To address this aim, migratory capacity, proangiogenic cytokine release and apoptotic susceptibility of CD3⁺/CD31⁺ and CD3⁺/CD31^? cells were determined. Human CD3⁺/CD31⁺ and CD3⁺/CD31^?cells from peripheral blood were isolated using magnetic-activated cell sorting. CD3⁺/CD31⁺ cells demonstrated significantly higher (～60%) migratory capacity to the chemokines SDF-1α (655 ± 99 vs. 273 ± 54 AU) and VEGF (618 ± 99 vs. 259 ± 57 AU) vs. CD3⁺/CD31^? cells. Release of angiogenic cytokines G-CSF, interleukin-8 and matrix metallopeptidase-9 were all ～100% higher (P < 0.05) in CD3⁺/CD31⁺ than CD3⁺/CD31^? cells. CD3⁺/CD31⁺ cells exhibited significantly higher intracellular concentrations of active caspase-3 (2.61 ± 0.60 vs. 0.34 ± 0.09 ng/mL) and cytochrome-c (21.8 ± 1.4 vs. 13.7 ± 1.0 ng/mL). In summary, CD3⁺/CD31⁺ cells have greater migratory and angiogenic cytokine release capacity, but are more susceptible to apoptosis compared with CD3⁺/CD31^? cells. Enhanced migratory capacity and angiogenic cytokine release may contribute to the vasculogenic properties of this unique T cell subpopulation.     

Expression of interferon-g and interleukin-4 production in CD4+ T cells in patients with chronic heart failure

The prevalence of inflammation is high among patients with chronic heart failure (CHF). Reduced ejection fraction was associated with frequency of CD4⁺ T cells of leukocytes. Therefore, we investigated inflammatory cytokines of expression markers in CD4⁺ T cells in patients with CHF. Blood samples were obtained from 103 patients with CHF, from 83 patients with stable angina (SA), and from 57 controls. Interferon-γ (IFN-γ)-positive CD4⁺ T cells and interleukin-4 (IL-4)-positive CD4⁺ T cells were analyzed using 3-color flow cytometry. The frequency (%) of IFN-γ-positive CD4⁺ T cells increased in patients with CHF compared with those with SA and controls (CHF: 28.3 ± 13.8, SA: 23.50 ± 10.38, controls: 19.00 ± 7.45, P < 0.001). There was no significant difference in the frequency of IL-4-positive CD4⁺ T cells among the three groups. The frequencies of CD4⁺ T cells that stained for IFN-γ decreased from 32.37% ± 16.40% on admission to 26.91% ± 12.53% after 2 weeks in 26 patients with CHF. B-type natriuretic peptide (pg/ml) and high-sensitivity C-reactive protein (mg/dl) levels decreased from 251.7 ± 150.4 and 0.64 ± 0.78 on admission to 208.2 ± 166.4 and 0.36 ± 0.34 after 2 weeks in the 26 patients with CHF. We have demonstrated expression of IFN-γ production of CD4⁺ T cells during CHF. Prevention of unwanted T cell activation could represent a new target in the treatment of CHF.     

The association between circulating endothelial progenitor cells and coronary collateral formation

Aim

We investigated the relationship between coronary collateral formation and circulating endothelial progenitor cells (EPC) in patients undergoing coronary angiography.

Methods and results

Circulating CD133⁺/34⁺ and CD34⁺/KDR⁺ EPCs were determined in 68 patients (normal coronary vessels in 24 patients and coronary artery disease (CAD) in 44 patients) (age: 58.7 ± 10.1, 64.7% male). Circulating EPCs were higher among patients with normal coronary vessels compared to patients with CAD for CD133⁺/34⁺ (p < 0.05) and CD34⁺/KDR⁺ cells (p < 0.05). The number of EPCs were significantly greater in patients with good coronary collateral formation (p < 0.05). EPC count was independent predictor for coronary collateral formation after adjustment for other cardiovascular risk factors and extent of CAD (p = 0.037).

Conclusion

In patients with severe coronary stenosis, those with increased circulating EPCs had better collateral formation compared to those with lower EPC counts. Our findings implicate that in addition to presence of critical stenosis, intact response of bone marrow is necessary for collateral formation in CAD.     

Circulating progenitor cells and their interaction with platelets in patients with an acute coronary syndrome

CD34⁺ cells expressing KDR (CD34⁺/KDR⁺) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34⁺ and CD34⁺/KDR⁺ progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y₁₂ receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34⁺ and CD34⁺/KDR⁺ progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34⁺ and CD34⁺/KDR⁺ cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34⁺ (CD61⁺/CD34⁺) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR⁺ (CD61⁺/KDR⁺) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34⁺ cells and the CD61⁺/KDR⁺ conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR⁺ conjugates and CD34⁺ cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration.     

Increased CD4(+) CD69(+) CD25(-) T cells in patients with hepatocellular carcinoma are associated with tumor progression

Background and Aim: A new subset of Treg cells, CD4⁺CD69⁺CD25^‐ T cells, has been identified in mice. Herein, we aimed to identify this subset of T cells and to evaluate its function in patients with hepatocellular carcinoma (HCC). Methods: We detected CD4⁺CD69⁺CD25^‐ T cells and its expression of CCR6 and transforming growth factor‐β1 (TGF‐β1) in peripheral blood of 91 HCC patients, 38 chronic hepatitis patients and 34 healthy donors by flow cytometry. CD4⁺CD69⁺CD25^‐ T cells in HCC tissues were also analyzed. Results: CD4⁺CD69⁺CD25^‐ T cells were significantly increased in peripheral blood of HCC patients compared with healthy persons and chronic hepatitis patients (8.74% ± 0.42% vs 4.55% ± 0.33% and 5.15% ± 0.36%, P < 0.0001). The percentage of peripheral CD4⁺CD69⁺CD25^‐ T cells was significantly higher in HCC patients with Tumor Node Metastasis (TNM) stage III plus IV (P < 0.05). Patients with large tumor size and tumor vascular invasion were inclined to obtain high percentage of CD4⁺CD69⁺CD25^‐ T cells (P < 0.05). The frequency of membrane‐bound TGF‐β1 positive cells in CD4⁺CD69⁺CD25^‐ T cells from HCC patients was higher than that from the other two groups (P < 0.0001). A considerable proportion of CD4⁺CD69⁺CD25^‐ T cells were present in HCC tissues, which has significant correlation with tumor size and TNM stage. Few CD4⁺CD69⁺CD25^‐ T cells express CCR6 both in peripheral blood and tumor tissues from HCC patients. Conclusions: Increased CD4⁺CD69⁺CD25^‐ T cells in HCC patients are significantly correlated with tumor size, vascular invasion and TNM stage. Thus, increased CD4⁺CD69⁺CD25^‐ T cells exert a critical role in HCC progression and might be a clinically aggressive phenotype of HCC.     

CD4+Foxp3+ T cells,interleukin-35 (IL-35) and IL-10 in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo evaluate three subtypes of CD4⁺Foxp3⁺ T cells, interleukin-35 (IL-35) and IL-10 in systemic lupus eryhtematosus (SLE) patients and study their relation to disease activity.Patients and methodsFifty SLE patients were included and divided according to the SLE disease activity index (SLEDAI) into 2 equal groups with activity or in remission. Twenty healthy subjects were included as controls. All subjects underwent flow cytometric analysis of CD4, CD25, CXCR5 and Foxp3 expression on T cells. Serum IL-35 and IL-10 levels were measured by ELISA.ResultsPatients were 46 females and 4 males with a mean age of 38.0 ± 10.0 years, disease duration of 9.2 ± 6.0 years. The mean SLEDAI was 6.8 ± 3.7 in active ones. SLE patients especially those with activity had significantly reduced percents of CD4⁺CD25⁺Foxp3⁺ and CD4⁺CXCR5⁺Foxp3⁺ T cells, but increased percents of CD4⁺CD25⁻Foxp3⁺ T cells. This was accompanied by significant higher levels of serum IL-35 and IL-10 (p < 0.0001). The SLEDAI in active patients significantly correlated with CD4⁺CD25⁻Foxp3⁺ T cell percent, serum IL-35 and IL-10 levels (p < 0.05) and inversely with the CD4⁺CD25⁺Foxp3⁺ and CD4⁺CXCR5⁺Foxp3⁺ T cell percents (p < 0.05). At cut-off values of 3.29% for CD4⁺CD25⁺Foxp3⁺ T cell, 7.62% for CD4⁺CD25⁻Foxp3⁺ T cell, 1.77% for CD4⁺CXCR5⁺Foxp3⁺ T cell, 22.04 pg/ml for IL-35 level and 30.51 pg/ml for serum IL-10 level were found to be highly sensitive and specific for detecting lupus activity.ConclusionCD4⁺Foxp3⁺ T cells, IL-35 and IL-10 showed high sensitivity and specificity for detecting SLE activity and may be considered as potentially promising therapeutic targets.     

Expansion of CD4+CD25+FoxP3+ regulatory T cells in hepatitis C virus‐related chronic hepatitis,cirrhosis and hepatocellular carcinoma

Aim: Regulatory T (Treg) cells may play a pivotal role in the persistence of hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). Therefore, we examined their frequency in peripheral blood from patients with HCV‐positive chronic hepatitis (CH), cirrhosis (LC) and HCC. Methods: Treg cells were identified as CD4⁺, CD25⁺ and FoxP3⁺ T lymphocytes using three‐color FACS. The frequency of Treg cells was expressed as a percentage of the total CD4⁺ T lymphocytes, and the phenotype of Treg cells was examined using CD45RA. Results: Treg cells were significantly increased in CH (5.88 ± 0.19%, n = 76; P < 0.01), LC (6.10 ± 0.28%, n = 40; P < 0.001) and HCC (6.80 ± 0.30%, n = 57; P < 0.0001) compared to healthy control (5.13 ± 0.25%, n = 31). However, Treg cells were not increased with the progression of fibrosis or the grade of inflammations. Treg cells were slightly increased in early‐stage HCC (6.91 ± 0.40%) compared with advanced‐stage HCC (6.58 ± 0.39%), but these results were not statistically significant. In a serial examination, a distinct increase in Treg cells after local therapy for early‐stage HCC was a hallmark of early recurrence. Most expanded Treg cells in HCC were CD45RA^‐, suggesting that a memory‐type Treg population had differentiated in the periphery and not in the thymus. Conclusion: We observed an increase in Treg cells in HCV‐related chronic liver disease, particularly in HCC, and these cells were shown to be memory‐type Treg cells.     

Percutaneous coronary intervention with drug-coated balloon-only strategy combined with single antiplatelet treatment in patients at high bleeding risk: Single center experience of a novel concept

Objectives

At least 1 month of dual antiplatelet therapy is required after coronary stenting. The aim of this all-comers retrospective registry study was to assess the efficacy and safety of percutaneous coronary intervention (PCI) using drug-coated balloon (DCB) with single antiplatelet treatment (SAPT).

Methods

Between 2011 and 2020, 232 PCIs were performed in 172 patients using the DCB-only strategy and discharged with SAPT.

Results

The mean age of the patients was 75 ± 11 years and 59% were male. The clinical presentation was stable coronary artery disease (CAD) in 42% of the patients and acute coronary syndrome (ACS) in 58%. The lesions were mainly de novo (96%). The majority (58%) of treated lesions were in large coronary arteries (≥3.0 mm). Most (87%) of the patients were at high bleeding risk (HBR) with at least one major or two minor Academic Research Consortium (ARC) risk factors for bleeding. Periprocedural DAPT was used in 49% of the patients. The 12-month major adverse cardiac events (MACE, the composition of cardiovascular death, nonfatal myocardial infarction, and target-lesion revascularization) rate was 1.4% in stable CAD and 7.1% in ACS. The 12-month all-cause mortality after DBC only + SAPT strategy was 4.1% in stable CAD and 12.1% in ACS. The rate of ischemia-driven target lesion revascularisation (TLR) was 0% in stable CAD and 3.0% in ACS at 12 months. The 12-month rate of significant bleeding (BARC type 2-5) was 10.5%. There were no acute or subacute vessel closures.

Conclusions

Despite the aged patient population with comorbidities, the TLR, MACE, and bleeding rates were low with DCB-only PCI combined with SAPT. This novel approach could reduce the post-PCI bleeding risk in patients with CAD and HBR compared to stenting.     

Decreased CTLA4+ and Foxp3+ CD25highCD4+ Cells in Induced Sputum from Patients with Mild Atopic Asthma

BackgroundDetails of the comparisons between airway and peripheral blood regulatory T cells (Tregs) in patients with atopic asthma are still unclear. The objective of this study is to investigate the profiles of both airway and circulating Tregs in atopic asthma.MethodsWe measured the numbers of Tregs and eosinophils in induced sputum and peripheral blood in 28 patients with mild atopic asthma and compared these with numbers in 18 healthy controls. The frequency (%) of Tregs (surface CTLA4⁺, intracellular Foxp3⁺, and CTLA4⁺Foxp3⁺ on CD25^highCD4⁺ T cells) in sputum and blood was determined by intracellular 5-color flow cytometry. We also correlated the numbers with the level of airway hyperresponsiveness (AHR) in asthmatics.ResultsThe mean frequencies of cells expressing CTLA4⁺ (19.4 ± 2.1%, p = 0.075), Foxp3⁺ (16.4 ± 3.3%, p = 0.001), and CTLA4⁺Foxp3⁺ (7.0 ± 1.1%, p = 0.008) in induced sputum from asthmatics were significantly lower than controls (27.2 ± 3.7%, 37.4 ± 4.7%, and 18.2 ± 3.6%, respectively), whereas in peripheral blood, there was no inter-group difference in the frequencies of cells expressing CTLA4⁺ (7.1 ± 1.5% vs 5.7 ± 1.7%, p > 0.05), Foxp3⁺ (35.7 ± 3.2% vs 21.1 ± 3.9%, p > 0.05), and CTLA4⁺Foxp3⁺ (6.6 ± 1.5% vs 4.2 ± 1.0%, p > 0.05). Moreover, the frequency of CD25^highCD4⁺ cells expressing CTLA4⁺, but not Foxp3⁺, in induced sputum was associated with AHR (r = 0.60, p = 0.009) and airway eosinophilic inflammation (r = ? 0.60, p = 0.008) in asthmatics.ConclusionsAirway, but not circulating, Tregs are decreased in mild atopic asthmatics, and are negatively correlated to an increase of airway eosinophilic inflammation and AHR.     

Influence of dual antiplatelet therapy on mean platelet volume in patients with coronary artery disease undergoing percutaneous coronary intervention

Mean platelet volume (MPV) is a well-established marker of platelet activation, and recent studies have shown that platelet activation is central to the processes in the pathophysiology of coronary artery disease (CAD). The study population consisted of 45 patients with stable CAD who underwent successful percutaneous coronary intervention (PCI) with drug-eluting stents. We selected 45 age- and sex-matched control subjects without cardiovascular diseases who did not require antiplatelet therapy. Hematological test was performed 3 times within 1 month before DAPT (baseline), at 2 weeks after PCI (post PCI) and at 9 months after PCI (follow-up). Compared to control subjects, MPV was significantly larger in patients with CAD (10.0 ± 0.6 vs 10.7 ± 0.8 fl, p < 0.01) although there was no significant difference in white blood cell count, hemoglobin, and platelet count between the 2 groups. In patients with CAD, DAPT did not affect platelet count (19.3 ± 4.8 × 10⁴–18.9 ± 4.6 × 10⁴/μl) or MPV (10.7 ± 0.8–10.5 ± 0.9 fl) during the follow-up period. MPV remained to be higher at follow-up in patients with CAD despite DAPT compared to control subjects (10.1 ± 0.7 vs 10.5 ± 0.9 fl, p < 0.05). Our data suggested that MPV might not be suitable for monitoring the effects of DAPT on platelet activity in patients with CAD undergoing PCI.     

The CD4/CD8 ratio of infused CD19-CAR-T is a prognostic factor for efficacy and toxicity

CD4⁺ and CD8⁺ chimeric antigen receptor T cells (CAR-T) play different roles in the in vivo anti-tumour response, but the role of the CD4⁺/CD8⁺ ratio among infused CAR-T has not been clearly defined yet. We analysed leftovers from infused anti-CD19 CAR-T bags of 31 patients with aggressive B-cell lymphomas. The median ratio was 1.44, lower for brexu-cel compared to tisa-cel and axi-cel. The CAR+CD4⁺/CD8⁺ ratio was influenced by lactate dehydrogenase levels at apheresis, not by age, previous treatments or the CD4⁺/CD8⁺ ratio in peripheral blood. Patients with a response at 3 months after CAR-T (M3) had a lower CAR+CD4⁺/CD8⁺ ratio in the infused products compared to non-responders (ratio 0.74 vs. 2.47, p = 0.011). A CAR+CD4⁺/CD8⁺ ratio higher than the cut point of 1.12 was associated with an increased risk of treatment failure at M3 (OR 23.3, p = 0.012) and M6 (OR 10, p = 0.028). The median 6-month PFS was 76% for patients with a ratio lower than 1.12% vs. 31% for the others. The prognostic role of the CAR+CD4⁺/CD8⁺ ratio was independent of the costimulatory domain (CD28 vs. 4-1BB) of the product (OR 16.41, p = 0.041). Our data indicate a crucial role for CD8⁺ CAR-T and the CAR+CD4⁺/CD8⁺ ratio in predicting CAR-T efficacy.     

CD14 C(-260)T promoter polymorphism and prevalence of acute coronary syndromes

BACKGROUND: Inflammation and infection have been implicated in atherosclerosis and its complications. The CD14 receptor mediates monocyte activation by lipopolysaccharide (LPS) of Gram-negative bacteria. The aim of this study was to assess whether the C(-260)T polymorphism in the promoter of the CD14 receptor gene is associated with a higher prevalence of acute coronary syndromes (ACS) and severity of coronary atherosclerosis. METHODS: We studied 428 patients (mean age: 63+/-10 years, 67% men) consisting of 334 patients with coronary artery disease (CAD) and 94 patients with normal coronary arteriogram. Patients with CAD were subdivided in two groups: (1) no previous history of ACS (n=140; 64+/-9 years; 79% men) and (2) patients with a history of ACS (n=194; 64+/-10 years; 80% men). CD14 genotypes were determined by a Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism Analysis (RFLP) technique. RESULTS: Patients with a prior ACS had a significantly higher frequency of the T/T genotype than CAD patients without prior ACS (33% vs. 20%; P=0.009), even after multivariate analysis (odd ratio [OR] 1.8 [1.1-3.1]; confidence intervals [CI] 95%; P=0.023). T/T genotype was not significantly different in CAD patients without prior ACS compared to controls (20% vs. 22.3%; P=0.67), and there was no significant association between genotypes, or allele frequencies, and severity of CAD. CONCLUSIONS: The CD14 C(-260)T polymorphism is associated with a history of ACS and it may represent a genetically determined risk factor for the development of ACS and atheromatous plaque vulnerability in angina patients.     

Changes and clinical significance of CD8+CD122+ T cells in the peripheral blood of patients with ankylosing spondylitis

The aim of our study was to explore the relationship between circulating T cells and ankylosing spondylitis (AS) and to find the role of the CD8+CD122+ T cells in the pathogenesis and progression of AS. With the method of case-control design, flow cytometry was performed to quantitatively determine the percentage of circulating CD8⁺CD122⁺ T cells in peripheral blood mononuclear cells from established AS patients and age- and gender-matched healthy controls. Serum levels of inflammatory cytokines like interleukin-2, interleukin-10, interleukin-15, TGF-β1, and TNF-ɑ were detected by enzyme-linked immunosorbent assay. The t test was used to compare differences between groups, correlation analysis with Spearman rank test and Pearson correlation was performed. The percentage of circulating CD8⁺CD122⁺ T cells were significantly increased in AS patients compared with controls (Z = ? 4.917, P = 0.001). Plasma IL-2, IL-10, IL-15, TGF-β1, and TNF-ɑ levels between cases and controls were analyzed but no statistically significant differences were found. The percentage of circulating CD8⁺CD122⁺ T cells were not significantly different in the two groups of patients with AS whether they were treated or not. In addition, the percentage of circulating CD8⁺CD122⁺ T cells was positively correlated with disease duration, CRP, and ASDAS-CRP. The CD8⁺CD122⁺ T cells in the peripheral blood of AS patients may be involved in the development of AS, and they may coordinate regulate inflammation and immune dysregulation in patients with AS, which may play an important role in the pathogenesis and prognosis of AS.     

The Decreased CD4+CD25+ FoxP3+ T Cells in Nonstimulated Allergic Rhinitis Patients Sensitized to House Dust Mites

Objective. Regulatory (CD4⁺CD25⁺) T cells have been shown to play an important role in the development of allergic diseases. This study aims to investigate CD4⁺CD25⁺ T cells, Forkhead box P3 (FoxP3⁺ cells), and T-helper 1/T-helper 2 (Th1/Th2) cytokines in newly diagnosed allergic rhinitis (AR) patients. Methods. Altogether, 10 subjects with AR and 12 age-matched nonallergic healthy subjects were included in this study. CD4⁺CD25⁺ T cells, FoxP3⁺ T cells in peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry, and the Th1/Th2 cytokine levels were determined by cytometric bead array immunoassay in both PBMC supernatants and nasal lavage fluids. Results. The percentage of CD4⁺CD25⁺ T cells were significantly higher, whereas the percentage of FoxP3⁺ cells were lower in AR patients compared with healthy subjects. In PBMC culture supernatants, interleukin-10 (IL-10) levels were significantly lower (p = .012), whereas IL-4, IL-5, and tumor necrosis factor-α (TNF-α) levels in nasal lavage fluids were higher in AR patients compared with healthy subjects (p = .026, p = .015, p = .03, respectively). Conclusions. Our findings indicate that decrease in CD4⁺CD25⁺FoxP3⁺ T cell fraction and diminished levels of IL-10 are noteworthy without allergen stimulation in house dust mite AR patients.     

Increased CD4+CD16+ and CD4+CD56+ T cell subsets in Behçet's disease

Behçet's disease is a systemic vasculitis of unknown etiology. Various immune abnormalities have previously been shown in Behçet's disease. We investigated T lymphocyte subsets associated with cytotoxic activity and natural killer (NK) cells by flow cytometry in 37 patients with Behçet's disease, 38 healthy controls, and 17 diseased control patients. Compared to the healthy controls, CD4⁺CD16⁺ and CD4⁺CD56⁺ subsets were found to be higher in the Behçet's disease group as well as in the disease control group (CD4⁺CD16⁺: BD=5?±?3, DC=14?±?14, HC= 3?±?2, P=0.001; CD4⁺CD56⁺: BD=11?±?5, DC= 18?±?17, HC=8?±?6, P=0.01). CD8⁺CD16⁺ and CD8⁺CD56⁺ T cell subsets were at normal levels in Behçet's disease but found to be elevated in disease controls. Similarly, NK cells (CD16⁺CD56⁺) were high only in the disease control group. Significant increases in CD4⁺CD16⁺ and CD4⁺CD56⁺ cell subsets in Behçet's patients and disease controls suggest that T cell activation patterns of these subsets in Behçet's disease are similar to those in other inflammatory disorders.     

Circulating Endothelial Progenitor Cells as Markers for Severity of Ischemic Chronic Heart Failure

IntroductionDespite a high potential of endothelial progenitor cells (EPCs) for diagnostic purposes, the EPC role in developing ischemic chronic heart failure (CHF) has not been determined obviously.The objective of this study was to assess the counts of CD45⁺CD34⁺, CD45⁻CD34⁺, CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ phenotyped circulating EPCs of various subpopulations in patients with ischemic CHF.Methods and ResultsThe study involved 153 patients (86 male), aged 48–62 years, with angiographically proven coronary artery disease (CAD) and 25 healthy volunteers. CHF was diagnosed in 109 patients (71.2%). Mononuclear cell populations were phenotyped by flow cytofluorimetry. Cardiovascular risk factors, such as type 2 diabetes mellitus, hyperlipidemia, arterial hypertension, and adherence to smoking, may have a negative effect on circulating EPC counts in CAD patients regardless of the presence of CHF. The depletion of the CD14⁺CD309⁺- and CD14⁺CD309⁺Tie2⁺-phenotyped circulating EPC counts is associated with the severity of left ventricular dysfunction, whereas the CD45⁺CD34⁺- and CD45⁻CD34⁺-mononuclear cell counts are more representative of the severity of atherosclerotic coronary artery lesions.ConclusionThe authors found that New York Heart Association functional class of CHF, left ventricular ejection fraction <42%, the N-terminal pro–B-type natriuretic peptide level >554 pg/mL, and Е/Еm ratio >15 U had the highest predictive value for the depletion of the EPC count in CAD patients.     

Circulating CD56dim natural killer cells and CD56+ T cells that produce interferon‐γ or interleukin‐10 are expanded in asymptomatic,E antigen‐negative patients with persistent hepatitis B virus infection

Infection with hepatitis B virus (HBV) can result in spontaneous resolution or chronic infection, which can remain asymptomatic or can progress to cirrhosis and/or hepatocellular carcinoma. The host immune response is thought to be a major determinant of the outcome of HBV infection and virus‐specific cytotoxic T lymphocytes (CTL) can mediate immunity against the virus and cause liver pathology. Antigen‐nonspecific innate lymphocytes may also contribute to HBV infection and liver disease, therefore, we examined the frequencies, phenotypes, cytolytic activities and cytokine profiles of circulating natural killer (NK) cells, CD1d‐restricted invariant natural killer T (iNKT) cells and CD56⁺ T cells in 102 asymptomatic HBV‐infected patients and compared them with those in 66 uninfected control subjects. NK cells expressing low levels of CD56 (CD56^dim) and CD56⁺ T cells were significantly expanded in the circulation of HBV‐infected patients compared with control subjects. CD1d expression and iNKT cell frequencies were similar in both groups. Despite these expansions, we did not detect augmented natural or cytokine‐induced cytotoxicity in the HBV‐infected subjects. All lymphocyte populations studied produced interferon‐γ (IFN‐γ) significantly more frequently when taken from HBV‐infected patients compared with when taken from healthy controls. Additionally, NK cells from the patients more frequently produced interleukin‐10. As our HBV‐infected cohort consisted of asymptomatic patients with low viral loads, we propose that CD56^dim NK cells and CD56⁺ T cells control HBV infection by noncytolytic mechanisms.     

急性冠状动脉综合征患者外周血CD31~(bright)/Annexin V~+内皮微粒水平增高

目的 观察急性冠状动脉综合征患者与非冠心病患者外周血内皮微粒水平,探讨CD31bright/AnnexinV+内皮微粒与心血管危险因素的相关性.方法 急性冠状动脉综合征患者56例,非冠心病患者26例,采用流式细胞仪检测外周血CD31bright/Annexin V+内皮微粒水平.结果 与非冠心病患者比较,急性冠状动脉综合征患者外周血CD31bright/Annexin V+内皮微粒显著增加(P<0.01),而急性心肌梗死与不稳定型心绞痛亚组之间外周血CD31bright/Annexin V+内皮微粒水平无显著性差异(P>0.05).所有入选患者中,2型糖尿病患者外周血CD31bright/Annexin V+内皮微粒水平较非糖尿病患者显著升高(P<0.05);多因素回归分析显示,血清甘油三酯水平与外周血CD31bright/Annexin V+内皮微粒数量独立正相关(r=0.28,P<0.05).急性冠状动脉综合征组血清高敏C反应蛋白水平与外周血CD31bright/Annexin V+内皮微粒数量呈正相关(r=0.31,P<0.05).结论 急性冠状动脉综合征患者和糖尿病患者外周血CD31bright/Annexin V+内皮微粒增多,提示急性冠状动脉综合征患者和2型糖尿病患者内皮损伤严重.CD31bright/Annexin V+内皮微粒水平增高可能与血清甘油三酯和血清高敏C反应蛋白水平增高有关.