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1.
Young-Joon Kim Ha-Jung Kim Se Kyoo Jeong Seung-Hwa Lee Mi-Jin Kang Ho-Sung Yu Young-Ho Jung Ju-Hee Seo Byoung-Ju Kim Jinho Yu Seoung-Ju Park Yong-Chul Lee Soo-Jong Hong 《Allergy, asthma & immunology research》2014,6(1):83-88
Purpose
Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma.Methods
BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb.Results
Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen.Conclusions
sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell. 相似文献2.
Ester Rosári Raphaelli Dal Ben Carine Hartmann do Prado Talita Siara Almeida Baptista Moisés Evandro Bauer Henrique Luiz Staub 《Journal of clinical immunology》2013,33(4):876-879
Introduction
CD4+CD25+Foxp3+ regulatory T (Treg) cell dysfunction has been documented in various autoimmune disorders, but not in antiphospholipid syndrome (APS) so far.Methods
In this cross-sectional study, we aim to investigate CD4+CD25+Foxp3+ Treg cells, CD3+CD19? T cells and CD3?CD19+ B cells in patients with primary APS and healthy controls. Cell subtypes were immunophenotyped using specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti-Foxp3, anti-CD19 PE) and flow cytometry.Results
Twenty patients with APS and 20 age- and sex-matched controls were studied. The percentage of total lymphocytes, activated Th cells (CD4+CD25+), Treg cells and CD3?CD19+ B cells were found significantly lower in APS patients as compared to controls (all p?<?0.05).Conclusion
A dysfunction in CD4+CD25+Foxp3+ Treg cells may represent one of the mechanisms leading to autoimmunity in APS patients. The decreased number of CD3?CD19+ B cells of APS patients warrants further elucidation. 相似文献3.
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Boo-Young Kim Hyang Rim Park Ji-Hyeon Shin Sung Won Kim Jin Hee Cho Yong Jin Park Soo Whan Kim 《Allergy, asthma & immunology research》2014,6(6):558-566
Purpose
Serine protease inhibitors are involved in immune development, anti-inflammatory mechanisms, and tissue repair. In the present study, the serine protease inhibitor 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF) was evaluated for its prophylactic and therapeutic applications in a mouse model of allergic rhinitis (AR).Methods
BALB/c mice were divided into 5 groups: contol (CON), Dermatophagoides farinae (Derf), AR mice treated with AEBSF before sensitization (S), AR mice treated with AEBSF after challenge (C), and steroid groups. Derf was used as an allergen. AEBSF was administered before S or after C. Allergic symptom scores, eosinophil counts, proteolytic activity, interferon-γ, interleukin (IL)-10 levels and serum Derf-specific IgE levels were measured. T-bet, GATA-3, Foxp3, IL-13, and transforming growth factor (TGF)-β mRNA levels were determined using real-time polymerase chain reaction. CD4+CD25+Foxp3+ T cells were assessed using flow cytometry.Results
Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, IL-13 mRNA levels, and tissue eosinophil counts decreased in both the S and C groups (P<0.05). Additionally, the percentage of CD4+CD25+Foxp3+ T cells, IL-10 levels, and Foxp3 mRNA levels increased in the S and C groups compared with those in the Derf group (P<0.05). AEBSF treatment decreased the proteolytic activity in the S and C groups (P<0.05).Conclusions
Prophylactic and therapeutic treatment with AEBSF significantly reduces allergic airway inflammation and can induce regulatory T cells in a murine model of AR. 相似文献5.
Maciej Ciebiada Karolina Kasztalska Ma?gorzata Gorska-Ciebiada Marcin Barylski Pawel Gorski 《Archives of Medical Science》2013,9(3):555-560
Introduction
Regulatory T cells (Tregs, CD4 + CD25high Foxp3+) play a crucial role in allergy and other inflammatory diseases. However, the isolation of viable Tregs on the basis of intracellular expression of specific Forkhead Box Protein P3 (Foxp3) is difficult. In this study we checked if the expression of IL-7 receptor (CD127) on the Tregs could be a useful marker for isolation of viable Treg Foxp3+ cells.Material and methods
Twenty-five patients sensitized to grass pollen with allergic rhinitis (AR) and ten healthy subjects were included. We compared Foxp3 expression in different CD4+ T cell subsets by flow cytometry and we assessed the relationship between the expression of Foxp3 and CD127 within regulatory T cells.Results
Within the CD4+ lymphocytes 3.68 ±2.0% showed expression of Foxp3, 51.82 ±8.03% of CD4+CD25high were Foxp3 positive (Foxp3+), whereas 82.12 ±5.4% of CD4+CD25highCD127low were Foxp3+. High intracellular expression of Foxp3 correlated with low superficial CD127 expression (r = 0.42, p = 0.017). There were no significant differences regarding the analysed markers between AR patients and healthy controls.Conclusions
Regulatory T cells may be purified from the fresh peripheral blood as viable regulatory Foxp3 bright cells using CD4, high expression of CD25 and low expression of CD127 antigen. 相似文献6.
Aims
Natural CD4+CD25+ regulatory cells (nTregs) have been implicated in maintaining peripheral immune tolerance. This study aims to test whether immunotherapy using in vitro-expanded Treg (iTregs) could suppress allograft rejection in corneal transplantation model.Methods
Natural CD4+CD25+ T cells were freshly purified from naïve mice and expanded in vitro by culturing with anti-CD3/CD28-coated Dynabeads, interleukin (IL)-2 and transforming growth factor (TGF-β1). Suppression ability of iTregs was assayed by co-culturing with CD4+CD25− T cells (Teff) in vitro and by targeting corneal allograft rejection in vivo. Tracking of iTreg after adoptive transfer in vivo were examined by CFSE labeling.Results
Natural Treg cells were expanded by culturing with anti-CD3/CD28-coated Dynabeads in the presence of IL-2 and TGF-β1. Compared with nTregs, iTregs had similar expression of CD62L, and PD- L1, lower expression of CD69, higher levels of PD-1, CD25, and Foxp3. iTreg cells exerted stronger suppression function than natural Treg cells when cocultured with CD4+CD25− T cells in vitro and prevented fully MHC-mismatched corneal allograft rejection. Survival of iTreg cells could suppress alloimmune reaction and most prone to migrate to graft draining LNs and spleens. Moreover, maintaining CD25 expression on iTregs was indicative for preservation of allosuppression.Conclusion
Therapeutic use of in vitro-expanded CD4+CD25+ T cells may be a effective and safe tool for controlling allograft rejection and may help induce allograft tolerance. 相似文献7.
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Arismendi MI Kallás EG Santos BA Carneiro-Sampaio MM Kayser C 《Clinics (S?o Paulo, Brazil)》2012,67(5):425-429
OBJECTIVES:
The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages.MATERIALS AND METHODS:
The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry.RESULTS:
Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095±36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T-cell receptor excision circles counts and age (r = -0.846; p<0.001) as well as between the proportion of CD4+CD25+Foxp3+ T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4+CD25+Foxp3+ T cells and the amount of T-cell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02).CONCLUSIONS:
In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood. 相似文献9.
Bao-Xiang Zhang Jun-Cheng Lyu Hai-Bo Liu Dian-Qin Feng Dian-Cai Zhang Xing-Jie Bi Zhi-Wu Duan Gang Ding 《Yonsei medical journal》2015,56(1):196-203
Purpose
Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8+T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8+CLA+T cells might be underlying mechanism in AD.Materials and Methods
CD8+CLA+T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8+CLA+T cells were evaluated. The proliferative responses of CD8+CLA+T cells were assessed by flow cytometry, and the levels of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay.Results
Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8+CLA+T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8+CLA+T cells in AD. Meanwhile, the levels of TGF-β1 produced by Tregs were significantly lower in AD, and anti-TGF-β1 abolished such suppression.Conclusion
The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8+CLA+T cells, mediated by TGF-β1, plays an important role in the pathogenesis of AD. 相似文献10.
Purpose
To characterize the maturation of CD4+ regulatory T lymphocytes (Treg) and of cytokine productions in preterm infants during their first 16 months of life.Methods
The proportions of CD4+ Treg cells, their phenotypic characteristics, and the mitogen-induced cytokine productions by peripheral blood mononuclear cells (PBMC) were analysed in 26 very-preterm infants from 2 to 16 months of age, and compared to results obtained for 17 cord blood mononuclear cells (CBMC) from very-preterm infants, 12 from term infants and to blood samples from 40 adults.Results
High proportion of CD25+/highCD4+ Treg cells was found at birth in preterm CB with a gradual decreased afterwards. However, their percentage at 16 months of age was still higher than in term CB. In contrast to adults, preterm infants were characterized by excellent linear correlations between the proportions of CD25+/highCD4+ and CD25+/highFoxP3+ CD4+ or CD25+/highCD127low CD4+ or CD25+/highFoxP3+CD127low CD4+T lymphocytes. CD45RO+ and HLA-DR+ expressions were very low on preterm Treg and progressively increased with age. Functionally, preterm compared to term CBMC secreted in response to phytohaemagglutinin lower IFN-γ, higher IL-5 and similar IL-12p70, IL-10, IL-2 and IL-13 concentrations. IFN-γ, IL-12p70 and IL-10 productions were at 16 months still lower than those obtained for adultsConclusion
Preterm differed from term CBMC both by their proportion and phenotype of CD4+ Treg lymphocytes and by their cytokine secretions. Maturation occurred during infancy with similar IFN-γ secretion but with persistently higher proportion of CD4+ Treg cells in 1 year preterm infants compared to term neonates. 相似文献11.
Background
Surgery has been reported to suppress cell-mediated immunity; however, the detailed mechanisms responsible for this remain unclear. This study determined the expression of lymphocyte activation gene 3 (LAG-3) and programmed cell death 1 (PD-1) in lymphocytes following surgery for gastric cancer.Methods
LAG-3 and PD-1 expression on both CD4+ and CD8+ T cells obtained pre- and post-operatively from gastric cancer patients were evaluated by multicolor flow cytometry.Results
The total lymphocyte count decreased rapidly from preoperative levels, reaching a minimum on postoperative day 1 and remaining significantly decreased on days 3 and 7. PD-1+CD4+ T cells significantly increased, reaching a maximum on postoperative day 1 and remaining significantly elevated on day 3. PD-1+CD8+ T cells significantly increased and reached a maximum on day 7 before returning to the preoperative level on day 30. There were no statistically significant differences in the frequency of LAG-3+CD4+ or LAG-3+CD8+ T cells after surgery. There were significant positive correlations between PD-1 and LAG-3 expression on both CD4+ andCD8+ T cells.Conclusion
PD-1 and LAG-3 expression on both CD4+ and CD8+ T cells was up-regulated and might be related to impaired cell-mediated immunity after surgery for gastric cancer. 相似文献12.
B. Huang Q. T. Wang S. S. Song Y. J. Wu Y. K. Ma L. L. Zhang J. Y. Chen H. X. Wu L. Jiang W. Wei 《Inflammation research》2012,61(11):1229-1239
Objective
To further explore the mechanism of etanercept (ENT, rhTNFR:Fc) and methotrexate (MTX) in the combined treatment of rheumatoid arthritis (RA), we investigated whether thymic and splenic T-cell subsets and their related cytokines imbalance could be restored by ETN/MTX treatment.Methods
The effect of ETN/MTX on collagen-induced arthritis (CIA) was evaluated by arthritis scores, joint and spleen histopathology, as well as indices of thymus and spleen. T lymphocytes proliferation was determined by [3H]-TdR incorporation. Levels of TNF-α, LT-α, IL-1β, RANKL, IL-10, IL-17, IFN-γ and IL-6 were detected by enzyme linked immunosorbent assay. The subsets of T lymphocytes including CD4+, CD8+, CD3+CD4+, CD4+CD25+, CD4+CD62L+ and CD4+CD25+Foxp3+ cells were quantified using flow cytometry.Results
Combined administration of ETN/MTX significantly inhibited the proliferation of T lymphocytes, decreased serum IL-6, TNF-α, IL-1β, RANKL and macrophage supernatant IL-17, LT-α, increased serum IFN-γ and macrophage supernatant IL-10. Moreover, the combined administration could restore CD4+/CD8+ ratio and Treg cells of CIA thymus and spleen.Conclusion
Taken together, our findings suggest that ENT/MTX may modify the abnormal T lymphocytes balance from central to peripheral lymphoid organs, which may partially, explained the mechanism of the combined administration. 相似文献13.
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16.
Dorothy K. Sojka Angela Hughson Deborah J. Fowell 《European journal of immunology》2009,39(6):1544-1551
CTLA‐4 is constitutively expressed by CD4+CD25+Foxp3+ Treg but its precise role in Treg function is not clear. Although blockade of CTLA‐4 interferes with Treg function, studies using CTLA‐4‐deficient Treg have failed to reveal an essential requirement for CTLA‐4 in Treg suppression in vivo. Conditional deletion of CTLA‐4 in Foxp3+ T cells disrupts immune homeostasis in vivo but the immune processes disrupted by CTLA‐4 deletion have not been determined. We demonstrate that Treg expression of CTLA‐4 is essential for Treg control of lymphopenia‐induced CD4 T‐cell expansion. Despite IL‐10 expression, CTLA‐4‐deficient Treg were unable to control the expansion of CD4+ target cells in a lymphopenic environment. Moreover, unlike their WT counterparts, CTLA‐4‐deficient Treg failed to inhibit cytokine production associated with homeostatic expansion and were unable to prevent colitis. Thus, while Treg developing in the absence of CTLA‐4 appear to acquire some compensatory suppressive mechanisms in vitro, we identify a non‐redundant role for CTLA‐4 in Treg function in vivo. 相似文献
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18.
CD4+CD25+Foxp3+ regulatory T (Treg) cells can undergo both thymic selection and peripheral expansion in response to self peptides that are agonists for their T cell receptors (TCR). However, the specificity by which these TCR must recognize peptide:MHC complexes to activate Treg cell function is not known. We show that CD4+CD25+Foxp3+ Treg cells can mediate suppression in response to peptides that are only weakly cross‐reactive with the self peptide that induced their formation in vivo. Moreover, suppression could be efficiently activated by peptide analogs that were inefficient at inducing CD69 up‐regulation, and that also induced little or no proliferation of naïve CD4+CD25–Foxp3– T cells expressing the same TCR. These findings provide evidence that self peptide‐specific CD4+CD25+Foxp3+ Treg cells can exert regulatory function in response to self‐ and/or pathogen‐derived peptides with which they are only weakly cross‐reactive. 相似文献
19.
Cheng-Shi Wang Shou-Hou Liu Jin Peng Chen Tang Wei-Guo Zhu 《African health sciences》2015,15(4):1200-1203
Background
Unclear pathogenesis existed for nasopharyngeal carcinoma.Aims
to analyze the role of bile acids in the pathogenesis of nasopharyngeal carcinoma.Methods
20 healthy volunteers and 20 patients with nasopharyngeal carcinoma were enrolled between January 1st, 2013 and December 31st, 2014. ESI-QTOF-MS analysis of serum was performed to find altered bile acids components. The biological function of changed bile acids was investigated using in vitro experiment.Results
Compared with healthy volunteers, the level of DCA and GDCA exhibited higher abundance in patients with nasopharyngeal carcinoma (p<0.01). Furthermore, the biological function was investigated for the inhibition of DCA and GDCA towards the secretion of IL-10 by CD4+CD25− T cells. Both DCA and GDCA significantly inhibited the secretion of IL-10 by CD4+CD25− T cells. Furthermore, DCA+GDCA can show stronger inhibition towards the secretion of IL-10 than DCA and GDCA.Conclusion
The inhibition of IL-10 secretion by elevated DCA and GDCA components in nasopharyngeal carcinoma patients is the inducer for nasopharyngeal carcinoma. 相似文献20.
Xiao-xi Zhang Yong-chao Qiao Wan Li Xia Zou Yin-ling Chen Jian Shen Qin-yuan Liao Qiu-jin Zhang Lan He Hai-lu Zhao 《Immunologic research》2018,66(1):179-186
Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet β cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic β cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9-fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-β (TGF-β) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions. 相似文献