Objective To investigate the changes of CD4 + CD25 + Foxp3 + regulatory T cells( Treg) in peripheral blood of patients with acute exacerbation of COPD( AECOPD) , and analyze the relationship of CD4 + CD25 + Foxp3 + Treg with insulin resistance. Methods A total of 79 patients with AECOPD were divided into four groups according to disease severity( 11 cases in stage Ⅰ,31 cases in stage Ⅱ,28 cases in stage Ⅲ, an 9 cases in stage Ⅳ) .42 healthy volunteers were recruited as control. Fast blood glucose( FBG) and fast insulin( FINS) were measured for calculating the insulin resistance index. The CD4 + CD25 + Foxp3 + Treg were detected by flow cytometry. The relationship between the proportion and number of CD4 + CD25 + Foxp3 + Treg with insulin resistance was statistically analyzed. Results Compared with the healthy control group, the levels of FBG, FINS, and insulin resistance index in the AECOPD patients were significantly higher ( P lt; 0. 01, P lt; 0. 05) . The proportion and number of CD4 + CD25 + Foxp3 + Treg in peripheral blood decreased significantly( P lt; 0. 01, P lt; 0. 05) . The insulin resistance index increased with the severity of AECOPD while the proportion and number of CD4 + CD25 + Foxp3 + Treg in peripheral blood decreased. The insulin resistance index in the AECOPD patients of stage Ⅲ and Ⅳ were higher than those of stage Ⅰ and Ⅱ. The proportion and number of CD4 + CD25 + Foxp3 + Treg in the AECOPD patients of stage Ⅲ and Ⅳ were significantly lower than those of stage Ⅰ and Ⅱ. Both the proportion and number of CD4 + CD25 + Foxp3 + Treg were negatively correlated with insulin resistance ( r = - 0. 633, - 0. 871, P lt; 0. 01) . Conclusions CD4 + CD25 + Foxp3 + Treg cells might may play important role in modulating insulin resistance in AECOPD. The more serious the disease, the lower the CD4 + CD25 + Foxp3 + Treg and the worse insulin resistance.
Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis patients.
Objective To examine the expression of promoter CpG island methylation of Notch1 gene and explore the variable sites for DNA methylation in lung CD4 + T cells of asthmatic rat models.Methods An ovalbumin ( OVA) sensitized- challenged asthmatic rat model was established. Total T cells were isolated and CD4 + T lymphocytes were purified using magnetic beads. Twenty Wistar rats were randomly divided into a control group and an asthma group ( n = 10 in each group) . CD4 + T cells were isolated by immunomagnetic beads and identified by flow cytometry ( FCM) . Realtime PCR was employed to examine the mRNA expression of Notch1 gene in lung CD4 + T cells and the methylation level of Notch1 gene was examined by methylation-specific PCR. Results The mRNA expression of Notch1 in lung CD4 + T cells of the asthma group was 2. 254 ±0. 403 times as much as that of the control group. The total methylation level of asthma group was lower than that of the control group ( 0. 150 ±0. 108 vs. 0. 300 ±0. 667, P lt;0. 01) . Conclusion Promoter demethylation is one of the major mechanisms of Notch1 gene up-regulation in pathogenesis of asthma.
Objective To investigate the percentage of CD4+CD25+ Treg in peripheral blood of patients with severe multiple trauma and systemic inflammatory response syndrome（SIRS） and its effects on cellular immunity and secondary infection.Metheds Peripheral blood of 23 patients with severe multiple trauma was collected in 24 h after SIRS was diagnosed，and flow cytometry was used to determine the percentage of CD4+CD25+ Treg and CD4/CD8 ratio.Simultaneously，in order to explore the cell proliferation，silver staining was used to determine Ag-NORs of leukomonocyte in peripheral blood represented by IS%.In order to investigate the infection in patients，sputum and secretion sample were collected for bacteriological examination on 1 and 5 day after SIRS was established.Forty healthy volunteers were enrolled as control.Results Compared with the control，the percentage of CD4+CD25+ Treg was significant higher[（14.21±3.43）% vs（9.53±3.22），Plt;0.01] and the ratio of CD4/CD8 and IS% were significant lower in patients with severe multiple trauma[（5.94±0.66）% vs（6.74±0.95）%，（1.22±0.25）% vs（1.72±0.36）%，respectively，both Plt;0.01].In those patients（n=14） who developed secondary infection，Treg% was significant higher [（18.69±4.21）% vs（12.58±2.49）%，Plt;0.01]，while IS% and CD4/CD8 were significant lower [（5.79±0.68）% vs（6.15±0.57）%，（1.15±0.25）% vs（1.39±0.25）%，both Plt;0.01].compared to the patients without secondary infection Conlusion CD4+CD25+ Treg is valuable to estimate the cellular immunity and predict secondary infection in patients with severe multiple trauma.
Regulatory T cells (Treg) are critical for regulation of tolerance, control immune responses to self-antigens thereby preventing autoimmunity, and limiting responses to foreign antigens thereby minimizing T cell-mediated immunopathology. Recent data indicate that suppression of organ-specific autoimmunity is dependent on the antigen specificity of Treg. An emerging model of Treg action is that organ-specific Treg acquire suppressive activity through activation by dendritic cells expressing specific antigens. Thus, the efficacy of Treg-based therapy should be increased by using antigen-specific Treg rather than polyclonal Treg. It is necessary to identify relevant antigens and to expand antigen-specific Treg from polyclonal populations. Here, we discuss recent techniques for expansion of antigen-specific Treg, function and antigen specificity of Treg and the therapeutic potential of Treg in controlling autoimmune disease and inducing transplant tolerance.
ObjectiveTo investigate the expression of CD4+CD25highCD127lowTreg (Treg) and related cytokines in peripheral blood of COPD patients with pulmonary hypertension and explore its clinical significance. MethodsPeripheral blood lymphocytes and serum were collected from 65 COPD patients with chronic pulmonary hypertension (the CPH group) and 20 COPD patients with normal pulmonary artery pressure (the control group). Flow cytometry was used to detect the Treg/CD4+ T cells and calculate its ratio, enzyme-linked immunosorbent assay was used to detect the serum contents of interleukin (IL)-6,IL-10 and tumor necrosis factor α (TNF-α). ResultsTreg can be detected in the peripheral blood of patients of COPD with or without PH, however, the Treg ratio in the CPH group was significantly lower than that in the control group [(7.41±1.12)% vs. (9.04±2.11)%, P<0.05]. Compared with the control group, the IL-10 level was significantly lower [(4.47±0.88)pg/mL vs. (5.18±0.26)pg/mL], while IL-6and TNF-α contents were significantly higher in the CPH group [(7.49±0.95)pg/mL vs. (6.76±0.35)pg/mL, (28.61±9.16)pg/mL vs. (19.64±4.85)pg/mL, P<0.05]. There was a positive correlation between Treg ratio and serum IL-10 level (r=0.41, P<0.05), and negative correlation between Treg ratio and TNF-α or IL-6 contents (r=0.45 or 0.37,P<0.05). The Treg ratio of the patients with severe pulmonary hypertension was lower than that in the patients with mild pulmonary hypertension [(7.42±1.03)% vs. (10.47±2.55)%,P<0.05). ConclusionsContents of Treg and IL-10 decrease while IL-6 and TNF-α increase in peripheral blood of COPD patients with pulmonary hypertension. It suggests that Treg cells and related cytokines may involve in the pathogenesis and progression of CPH. Treg may becomea potential biological prognosis indicator and treatment target of CPH in the future.
Objective To investigate the expression of the histone deacetylases 1( HDAC1) and the level of whole histone acetylation and methylation in lung T cells of asthmatic rats, and investigate their role in the pathogenesis of asthma.Methods Sixteen wistar rats were randomly divided into a control group and an asthma group( n =8 in each group) . The rats was sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The asthmatic ratmodel was confirmed by measurement of pulmonary function, histochemical staining, HE staining, and the levels of interleukin-4 ( IL-4 ) , interferon-gamma ( IFN-γ) and immunoglobulin E( IgE) in serum and bronchoalveolar lavage fluid ( BALF) . T cells were isolated fromrat lungs and the purity was identified. The expression of the HDAC1, the level of whole histone H3 and H4 acetylation, and whole H3K9 dimethylation were analyzed by Western blot in lung T cells. Results Compared with the control group, the protein expression of HDAC1 was significantly lower( 0. 465±0. 087 vs 0. 790 ±0. 076, P lt;0. 05) in lung T cells of the asthma group. No significant differences werefound in regard to the level of whole histone H3 and H4 acetylation and whole H3K9 dimethylation betweenthe two groups. Conclusions HDAC1 in lung T cells may be involved in the pathogenesis of asthma.Histone modification by HDAC1 may be a specific eventwith gene transcription which may not be associated with asthma.
Objective To assess the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs). Methods We searched MEDLINE (1966 to November 2009), EMbase (from inception to September 2009), and The Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcome measures for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively. Results Forty-two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti-metabolism drugs, IL-2 receptor-blocking antibodies, T-cell depleting antibodies, and co-stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than those taking CNIs, but no differences were found in graft function (6-42-month follow-up). Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the larger number of the blood Tregs in the patients treated with Rapa does not show any correlation with better graft function. Large-sample and high-quality clinical studies with longer follow-up are needed to thoroughly assess the efficacy of immunosuppressive drugs on Tregs and to reveal whether a relationship exists between Tregs and graft function.
Objective To investigate the relationship between blood CD4 + CD25 + regulatory T cells ( Treg cells) and cell immunity in patients with sepsis and its prognostic value.Methods 27 patients with sepsis admitted during August 2007 and August 2008 in ICU were enrolled, while 40 healthy volunteers served as control. According to the clinical outcome after 28 days’ treatment, the sepsis patients were assigned to a death group( n=8) and a survival group ( n =19) . Blood Treg% and CD4 /CD8 were detected by flow cytometry and total AgNOR area/nucleus area per cell ( IS%) was measured by silver nitrate staining and image processing. Results The Treg% in the patients with sepsis was significant higher than that in the normal control [ ( 5. 61 ±1. 60) % vs. ( 0. 78 ±0. 23) % , P lt; 0. 01 ] , while the level of CD4 /CD8 and IS% were significant lower[ CD4 /CD8: ( 1. 09 ±0. 30) vs. ( 1. 71 ±0. 36) , IS% : ( 5. 19 ±1. 07) % vs. ( 6. 76 ±0. 92) % , both P lt; 0. 01] . Significant correlations were found between Treg% and CD4 /CD8( r= - 0. 484, P lt;0. 01) , and between Treg% and IS% ( r = - 0. 588, P lt;0. 01) . Compared with the survival group, Treg% was significant higher [ ( 7. 09 ±1. 17) % vs. ( 5. 00 ±1. 33) % , P lt; 0. 01] , and CD4 /CD8 and IS% were significant lower[ CD4 /CD8: ( 0. 87 ±0. 22) vs. ( 1. 18 ±0. 29) , IS% : ( 3. 97 ±0. 42) % vs. ( 5. 71 ±0. 81) % , both P lt; 0. 01] in the death group. Conlusion Blood Treg% level can reflect the cell immune state of patients with sepsis and is of clinical value to assess the prognosis.
Objective To summarize research progress of the mechanism of natural killer cells (NK cells) acted in regulating the T cell immunity in chronic infectious disease. Method Literatures about recent studies concerning how NK cells act as a regulator for T cells in chronic infectious disease were reviewed according to the results obtained from PubMed, Embase, CNKI, CBM, and Wanfang databases. Results NK cells that acted as regulators of T cell immunity could affect T cell immune responses through influencing antigen presentation, secreting cytokine, and presenting lytic activities, thus playing an important role in the immunological therapy of chronic infectious diseases. Conclusion NK cells are critical for T cell immune regulation, which could provide noval strategies for immunological therapy of chronic infectious disease, transplantation-related immune rejection, and autoimmune disease.