共查询到20条相似文献,搜索用时 15 毫秒
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Background
Both naturally arising Foxp3+ and antigen-induced Foxp3− regulatory T cells (Treg) play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy.Methodology/Principal Findings
Using a novel class II MHC tetramer, we have isolated a population of CD4+ Foxp3− T cells specific for the autoantigen glutamic acid decarboxylase p286–300 peptide (NR286 T cells) from diabetes-resistant non-obese resistant (NOR) mice. These Foxp3− NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-γ was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg.Conclusions/Significance
These studies identified a unique population of autoantigen-specific Foxp3− Treg that can exert their regulatory function dependent on not only IFN-γ and NO but also cell contact with target cells. 相似文献7.
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Victoria L. Green Anna Michno Nicholas D. Stafford John Greenman 《Cancer immunology, immunotherapy : CII》2013,62(5):863-873
Background
The nature of the tumour microenvironment immune response in head and neck cancer patients has an important role in tumour development and metastasis, but it is unknown if this differs between cancer subsites or whether it is related to the peripheral immune response.Methods
Immune cells (CD4, CD8, Foxp3) in head and neck squamous cell carcinoma tissue (HNSCC; n = 66), detected by immunohistochemistry, have been correlated with tumour subsite and immune cells in the peripheral circulation (CD4+CD25HighFoxp3+ Treg and CD4+ T cells), identified using flow cytometry.Results
Oropharyngeal tumours had a greater number of infiltrating immune cells in both tumour and stroma compared with other subsites, but no difference was observed in the circulating levels. Immune cells in the stroma were positively related to those in the tumour with consistently higher levels in stroma. A strong relationship was found between the number of CD4+ and Foxp3+ cells but not between the number of CD8+ and Foxp3+ cells in the tumour. The number of Foxp3+ cells within the tumour was positively correlated with the percentage of circulating CD4+CD25High cells positive for Foxp3. Late stage laryngeal tumours showed a higher number of Foxp3+ lymphocytes compared with early stage malignancies, and oropharyngeal tumours had more CD4+ cells in node negative tumours compared with node positive ones.Conclusion
The level of immune cell infiltration in head and neck squamous cell carcinoma appears to be subsite dependent residing primarily in the stroma and is likely to be dependent on the peripheral immune response. 相似文献9.
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To maintain a quiescent gut microenvironment, proper regulation of immune responses initiated by pro-inflammatory immune subsets is required. Several types of regulatory T cells are reported to exert pivotal roles in achieving this. Among various types of regulatory T cells, the crucial role of Foxp3+ Treg cells has been well documented. Furthermore, accumulating evidence demonstrates that both microbial and dietary factors influence the induction and suppressor functions of intestinal Foxp3+ Treg cells. Foxp3+ Treg cells are a highly activated T cell subset which responds rapidly to environmental and nutritional stimuli. Thus, sufficient nutrient supply is required to fuel the high energetic status of Foxp3+ Treg cells for the regulation of intestinal immunity. 相似文献
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Marieke A. van Leeuwen M. Fleur du Pré Roy L. van Wanrooij Lilian F. de Ruiter H. C. Raatgeep Dicky J. Lindenbergh-Kortleve Chris J. Mulder Lissy de Ridder Johanna C. Escher Janneke N. Samsom 《PloS one》2013,8(7)
Background
Celiac disease (CD) is an intestinal inflammation driven by gluten-reactive CD4+ T cells. Due to lack of selective markers it has not been determined whether defects in inducible regulatory T cell (Treg) differentiation are associated with CD. This is of importance as changes in numbers of induced Treg could be indicative of defects in mucosal tolerance development in CD. Recently, we have shown that, after encounter of retinoic acid during differentiation, circulating gut-imprinted T cells express CD62LnegCD38+. Using this new phenotype, we now determined whether alterations occur in the frequency of natural CD62L+Foxp3+ Treg or mucosally-imprinted CD62LnegCD38+Foxp3+ Treg in peripheral blood of CD patients. In particular, we compared pediatric CD, aiming to select for disease at onset, with adult CD.Methods
Cell surface markers, intracellular Foxp3 and Helios were determined by flow cytometry. Foxp3 expression was also detected by immunohistochemistry in duodenal tissue of CD patients.Results
In children, the percentages of peripheral blood CD4+Foxp3+ Treg were comparable between CD patients and healthy age-matched controls. Differentiation between natural and mucosally-imprinted Treg on the basis of CD62L and CD38 did not uncover differences in Foxp3. In adult patients on gluten-free diet and in refractory CD increased percentages of circulating natural CD62L+Foxp3+ Treg, but normal mucosally-imprinted CD62LnegCD38+Foxp3+ Treg frequencies were observed.Conclusions
Our data exclude that significant numeric deficiency of mucosally-imprinted or natural Foxp3+ Treg explains exuberant effector responses in CD. Changes in natural Foxp3+ Treg occur in a subset of adult patients on a gluten-free diet and in refractory CD patients. 相似文献14.
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Naozumi Ishimaru Takeshi Nitta Rieko Arakaki Akiko Yamada Martin Lipp Yousuke Takahama Yoshio Hayashi 《PloS one》2010,5(1)
Background
Migration of T cells, including regulatory T (Treg) cells, into the secondary lymph organs is critically controlled by chemokines and adhesion molecules. However, the mechanisms by which Treg cells regulate organ-specific autoimmunity via these molecules remain unclear. Although we previously reported autoimmune exocrinopathy resembling Sjögren''s syndrome (SS) in the lacrimal and salivary glands from C-C chemokine receptor 7 (CCR7)-deficient mice, it is still unclear whether CCR7 signaling might specifically affect the dynamics and functions of Treg cells in vivo. We therefore investigated the cellular mechanism for suppressive function of Treg cells via CCR7 in autoimmunity using mouse models and human samples.Methods and Findings
Patrolling Treg cells were detected in the exocrine organs such as lacrimal and salivary glands from normal mice that tend to be targets for autoimmunity while the Treg cells were almost undetectable in the exocrine glands of CCR7 −/− mice. In addition, we found the significantly increased retention of CD4+CD25+Foxp3+ Treg cells in the lymph nodes of CCR7 −/− mice with aging. Although Treg cell egress requires sphingosine 1-phosphate (S1P), chemotactic function to S1P of CCR7−/− Treg cells was impaired compared with that of WT Treg cells. Moreover, the in vivo suppression activity was remarkably diminished in CCR7 −/− Treg cells in the model where Treg cells were co-transferred with CCR7 −/− CD25-CD4+ T cells into Rag2 −/− mice. Finally, confocal analysis showed that CCR7+Treg cells were detectable in normal salivary glands while the number of CCR7+Treg cells was extremely decreased in the tissues from patients with Sjögren''s syndrome.Conclusions
These results indicate that CCR7 essentially governs the patrolling functions of Treg cells by controlling the traffic to the exocrine organs for protecting autoimmunity. Characterization of this cellular mechanism could have clinical implications by supporting development of new diagnosis or treatments for the organ-specific autoimmune diseases such as Sjögren''s syndrome and clarifying how the local immune system regulates autoimmunity. 相似文献17.
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Qing Li Yi Wang Yiping Wang Ke Chen Qing Zhou Wei Wei Yuan Wang 《Cell biochemistry and biophysics》2014,70(2):1489-1498
The imbalance of CD4+CD25+ regulatory T (Treg) cells and Th17 cells has shown to be involved in pathogenesis of atherosclerosis and acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)]. The purpose of this study is to explore the significance of Treg/Th17 ratio in early diagnosis for ACS. We detected expression of Treg and Th17 in patients with AMI, UA, stable angina, and subjects with normal coronary arteries at the time of admission. Our results showed that ACS patients have a significant increase of Th17 number, but a marked decline of Treg/Th17 ratio, Treg number, and Treg function. Significant positive correlations in Th17 frequency and negative correlation in Treg frequency, Treg/Th17 ratio were found to levels of oxidized low-density lipoprotein (Ox-LDL), high sensitive C-reactive protein (hsCRP), Lipoprotein (a) [Lp(a)], and Creatine kinase-MB(mass) (CK-MBmass) in serum. Receiver-operating characteristic curves shown that the predictive specificity and sensitivity of Treg/Th17 ratio for ACS and AMI was the highest among all the five markers: Ox-LDL, hsCRP, Lp(a), CK-MBmass, and Treg/Th17 ratio. In conclusion, Treg/Th17 ratio appeared to be a novel indicator for early diagnosis of ACS. 相似文献