scholarly journals The Effect of Citrus Peel Extracts on Cytokines Levels and T Regulatory Cells in Acute Liver Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ia Pantsulaia ◽  
Manana Iobadze ◽  
Nato Pantsulaia ◽  
Tinatin Chikovani
Keyword(s):  
T Cell ◽  
Liver Injury ◽  
Immune Responses ◽  
Autoimmune Hepatitis ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Hepatocellular Injury ◽  
Citrus Peel ◽  
Anti Inflammatory

Background. T cell-mediated immune responses contribute to the hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of antioxidant, anti-inflammatory mixture of citrus peel extract (CPE) on the immune-mediated liver injury.Methods. The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring frequency of T regulatory cells (Tregs), cytokines (TNF-α, IL-10, and IFN-γ), and nitric oxide levels.Results. The CPE application notably prevents development of liver injury through decreasing levels of both cytokines (TNF-alpha, INF) and regulatory T cells and increasing levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in evident reduction of the liver damage.Conclusion. Our findings represent the primary preclinical data indicating that the CPEin vivocould ameliorate Con A induced hepatitis. The low dose of CPE most likely can be used for the treatment of the T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis.

scholarly journals Histone/protein deacetylases and T-cell immune responses

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2443-2451 ◽  
Author(s):  
Tatiana Akimova ◽  
Ulf H. Beier ◽  
Yujie Liu ◽  
Liqing Wang ◽  
Wayne W. Hancock
Keyword(s):  
T Cell ◽  
Cell Biology ◽  
T Regulatory Cells ◽  
Hdac Inhibitors ◽  
Experimental Studies ◽  
Cell Subset ◽  
Histone Protein ◽  
Anti Inflammatory

Abstract Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3+ T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.

CD4+CD25+ T Cells Can Inhibit CD8 T Cell Mediated GVHD: Requirement for In Vivo Recognition of Allogeneic Host MHC Class II Antigens.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1307-1307
Author(s):  
Robert B. Levy ◽  
Angela Jones
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
T Regulatory Cells ◽  
Cd8 T Cell ◽  
Class Ii ◽  
Regulatory Cells

Abstract CD4 regulatory T (Treg) cells have shown promise in the transplantation mileu including the ability to inhibit the development of graft vs host disease (GVHD) following allogeneic hematopoietic stem cell transplants (HCT). The antigen specificity of the Treg population(s) involved is not yet clear nor is the role of their activation following transplant. We are interested in determining the requirement for recognition of host MHC antigens following infusion of CD4+CD25+ T cells in an experimental model of GVHD. To clearly distinguish the requirements of regulatory vs GVH reactive cells, a model of CD8 T cell mediated GVHD was developed using highly purified BALB/c (H2d) donor CD8+ T cells (Miltenyi column, 95-98%). CD8 T cells were transplanted together with T cell depleted (TCD) BALB/c BMC into 12.0 GY (6.0 Gy split dose) TBI conditioned C57BL/6 (B6, H2b) recipients. To support development of GVHD by these cells, resistance was inhibited by treatment of recipients with anti-NK1.1mab (PK136) at Days -1, 0 and +7. BALB/c CD8+ T cells at doses of 5.0x106 but not 2.5x106 induced weight loss and some lethality in B6 recipients. 5x106 CD8+ T cells were then transplanted into B6-MHC class II−/ − recipients. GVHD symptoms including weight loss and lethality were readily apparent in these mice post-transplant. Interestingly, GVHD was consistently more severe with respect to the induction of weight loss and lethality in MHC Class II−/ − vs B6-wt recipients. Highly enriched BALB/c CD4+CD25+ T cells (> 95%) were produced from spleen and lymph node cells following negative (B-cells, CD8 and NK) and positive (CD25) selection using Miltenyi magnetic bead columns. Co-transplant of 1x106 CD4+CD25+ T cells together with BALB/c CD8+ T cells into B6 recipients inhibited GVHD as assessed by the absence of weight loss and lethality compared to B6 recipients of CD8+ T cells alone. In contrast, BALB/c CD4+CD25+ T cells failed to protect B6-MHC class II−/ − recipients from severe CD8+ T cell mediated GVHD. These findings demonstrate that donor CD4+ T regulatory cells can suppress GVHD inducing CD8+ T cells after the former recognize host class II alloantigen following transplant. We hypothesize that activated CD4+CD25+ T regulatory cells inhibit GVH reactive T cells at the host APC interface. Future studies in this model can be designed to examine ex-vivo activated and expanded CD4+CD25+ T regulatory populations. Transplant of such cells will enable us to address questions regarding the importance of in vivo recognition of host class II in the regulation of GVHD by these cells.

scholarly journals IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25

2010 ◽  
Vol 107 (5) ◽  
pp. 2171-2176 ◽  
Author(s):  
Sven Létourneau ◽  
Ester M. M. van Leeuwen ◽  
Carsten Krieg ◽  
Chris Martin ◽  
Giuseppe Pantaleo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Biological Activity ◽  
T Cell ◽  
T Regulatory Cells ◽  
T Cell Proliferation ◽  
Regulatory Cells ◽  
T Cell Homeostasis ◽  
Α Subunit ◽  
Deficient Mice

IL-2 is crucial to T cell homeostasis, especially of CD4+ T regulatory cells and memory CD8+ cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor α (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2–mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.

scholarly journals Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo

Immunology ◽  
2004 ◽  
Vol 113 (4) ◽  
pp. 499-508 ◽  
Author(s):  
Monika Gad ◽  
Nanna N. Kristensen ◽  
Evelyn Kury ◽  
Mogens H. Claesson
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Regulatory Cells ◽  
T Cell Responses ◽  
Regulatory Cells ◽  
Cell Responses ◽  
Immature Dendritic Cells

scholarly journals Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies

2019 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo
Keyword(s):  
T Regulatory Cells ◽  
In Vivo Studies ◽  
Low Grade ◽  
Regulatory Cells ◽  
Grape Polyphenols ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Red Grape

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

scholarly journals Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 35 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo
Keyword(s):  
T Regulatory Cells ◽  
Antioxidant Properties ◽  
In Vivo Studies ◽  
Low Grade ◽  
Regulatory Cells ◽  
Grape Polyphenols ◽  
Anti Inflammatory ◽  
Red Grape

In this review, special emphasis will be placed on red grape polyphenols for their antioxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of proinflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Additionally, the effects of red grape polyphenols will be analyzed in obesity, as a low-grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood–brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great antioxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites, and interaction with microbiota, deserve deeper studies.

scholarly journals Suppression of the Immune Response Against Tuberculosis by Natural T Regulatory Cells

2021 ◽  
Author(s):  
◽  
Kylie Margaret Quinn
Keyword(s):  
Immune Responses ◽  
Plasmid Dna ◽  
T Regulatory Cells ◽  
Protective Efficacy ◽  
Mycobacterial Infection ◽  
Bcg Vaccine ◽  
Regulatory Cells ◽  
Correlates Of Protection ◽  
Immune Correlates

<p>The causative agents of Tuberculosis (Tb), Mycobacterium tuberculosis and Mycobacterium bovis, subvert a number of host immune mechanisms to promote persistence of infection in the human host. Infection with these immunoevasive pathogens is estimated to cause 1.8 million deaths per year. The only Tb vaccine currently available is an attenuated form of M. bovis, called bacille Calmette Guerin (BCG), and its efficacy is highly variable. Thus, development of more effective vaccine strategies for Tb is of significant importance. Host-derived natural CD4+CD25+ T regulatory cells (Tregs) suppress host immune responses and prevent autoimmunity. However, Tregs can also interfere with protective immune responses against chronic infections or with the protective efficacy of vaccines. There is speculation that mycobacteria exploit the suppressive activity of Tregs to permit persistence in the host and that Treg activity also diminishes the protective efficacy of the BCG vaccine. Therefore, to explore the role of Tregs in anti-mycobacterial immunity, I first optimised a protocol to inactivate Tregs in vivo in a murine model, through administration of anti-CD25 monoclonal antibody. In addition, I developed a novel plasmid DNA replicon vaccine against Tb to aid with the assessment of the effect of Tregs on Tb vaccines. I hypothesised that inactivating Tregs in vivo prior to mycobacterial infection would enhance acute immune responses that are thought to be protective under current dogma and thereby enhance bacterial clearance. Enhanced immune responses were observed but, contrary to the hypothesis, inactivation of Tregs did not alter bacterial numbers in the lung. I also hypothesised that inactivating Tregs in vivo prior to live BCG or DNA vaccination would enhance primary and secondary immune responses that are thought to be protective against Tb infection and thereby enhance the protective efficacies of the vaccines. Enhanced vaccine-induced immune responses and accelerated secondary immune responses were observed for the BCG vaccine. However, Treg inactivation did not alter the protective efficacy of the BCG vaccine, and preliminary data suggests Treg inactivation may in fact decrease the protective efficacy of one plasmid DNA vaccine tested. In summary, this thesis illustrates that inactivating natural Tregs does not enhance protection from mycobacterial infection. This implies that inactivation of natural Tregs cannot be used in a therapeutic setting to enhance treatment or vaccination approaches for Tb. More importantly, Treg inactivation enhances immune responses that current dogma regard as protective against Tb infection, but does not correspondingly enhance protection. As a result of this disparity, this thesis questions the validity of measures that are commonly used as immune correlates of protection for Tb vaccine design. Ultimately, the development of more accurate immune correlates of protection for Tb will permit targeted design of more effective Tb vaccination strategies.</p>

scholarly journals Suppression of the Immune Response Against Tuberculosis by Natural T Regulatory Cells

2021 ◽  
Author(s):  
◽  
Kylie Margaret Quinn
Keyword(s):  
Immune Responses ◽  
Plasmid Dna ◽  
T Regulatory Cells ◽  
Protective Efficacy ◽  
Mycobacterial Infection ◽  
Bcg Vaccine ◽  
Regulatory Cells ◽  
Correlates Of Protection ◽  
Immune Correlates

<p>The causative agents of Tuberculosis (Tb), Mycobacterium tuberculosis and Mycobacterium bovis, subvert a number of host immune mechanisms to promote persistence of infection in the human host. Infection with these immunoevasive pathogens is estimated to cause 1.8 million deaths per year. The only Tb vaccine currently available is an attenuated form of M. bovis, called bacille Calmette Guerin (BCG), and its efficacy is highly variable. Thus, development of more effective vaccine strategies for Tb is of significant importance. Host-derived natural CD4+CD25+ T regulatory cells (Tregs) suppress host immune responses and prevent autoimmunity. However, Tregs can also interfere with protective immune responses against chronic infections or with the protective efficacy of vaccines. There is speculation that mycobacteria exploit the suppressive activity of Tregs to permit persistence in the host and that Treg activity also diminishes the protective efficacy of the BCG vaccine. Therefore, to explore the role of Tregs in anti-mycobacterial immunity, I first optimised a protocol to inactivate Tregs in vivo in a murine model, through administration of anti-CD25 monoclonal antibody. In addition, I developed a novel plasmid DNA replicon vaccine against Tb to aid with the assessment of the effect of Tregs on Tb vaccines. I hypothesised that inactivating Tregs in vivo prior to mycobacterial infection would enhance acute immune responses that are thought to be protective under current dogma and thereby enhance bacterial clearance. Enhanced immune responses were observed but, contrary to the hypothesis, inactivation of Tregs did not alter bacterial numbers in the lung. I also hypothesised that inactivating Tregs in vivo prior to live BCG or DNA vaccination would enhance primary and secondary immune responses that are thought to be protective against Tb infection and thereby enhance the protective efficacies of the vaccines. Enhanced vaccine-induced immune responses and accelerated secondary immune responses were observed for the BCG vaccine. However, Treg inactivation did not alter the protective efficacy of the BCG vaccine, and preliminary data suggests Treg inactivation may in fact decrease the protective efficacy of one plasmid DNA vaccine tested. In summary, this thesis illustrates that inactivating natural Tregs does not enhance protection from mycobacterial infection. This implies that inactivation of natural Tregs cannot be used in a therapeutic setting to enhance treatment or vaccination approaches for Tb. More importantly, Treg inactivation enhances immune responses that current dogma regard as protective against Tb infection, but does not correspondingly enhance protection. As a result of this disparity, this thesis questions the validity of measures that are commonly used as immune correlates of protection for Tb vaccine design. Ultimately, the development of more accurate immune correlates of protection for Tb will permit targeted design of more effective Tb vaccination strategies.</p>

scholarly journals Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000873 ◽  
Author(s):  
Mateusz Gliwiński ◽  
Dorota Iwaszkiewicz-Grześ ◽  
Anna Wołoszyn-Durkiewicz ◽  
Monika Tarnowska ◽  
Magdalena Żalińska ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Immune Responses ◽  
T Regulatory Cells ◽  
Cell Receptor ◽  
Regulatory Cells ◽  
Antigen Specificity ◽  
Adoptive Therapy

ObjectiveHere we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets.Research design and methodsWe compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs.ResultsPatients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vβ/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures.ConclusionsT1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs.Trial registration numberEudraCT 2014-004319-35.

scholarly journals The Role of CD4 T Cells in the Pathogenesis of Murine AIDS

2006 ◽  
Vol 80 (12) ◽  
pp. 5777-5789 ◽  
Author(s):  
Wen Li ◽  
William R. Green
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nude Mice ◽  
Cd4 T Cells ◽  
T Regulatory Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Regulatory Cells ◽  
Murine Aids

ABSTRACT LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD154 on CD4 T cells with CD40 on B cells. However, it is not clear which additional characteristics of the phenotypically and functionally heterogeneous CD4 T-cell compartment are required. Here, in vivo adoptive transfer experiments using B6.nude recipients are employed to compare the pathogenic abilities of CD4 T-cell subsets defined on the basis of cell surface phenotypic or functional differences. Th1 and Th2 CD4 T cells equally supported MAIDS induction. The rare Thy1.2 − CD4 subset that expands upon LP-BM5 infection was not necessary for MAIDS. Interestingly, CD45RBlow CD4 T cells supported significantly less disease than CD45RBhigh CD4 T cells. Because the decreased MAIDS pathogenesis could not be attributed to inhibition by CD45RBlow CD25+ natural T-regulatory cells, an intrinsic property of the CD45RBlow cells appeared responsible. Similarly, there was no evidence that natural T-regulatory cells played a role in LP-BM5-induced pathogenesis in the context of the intact CD4 T-cell population.

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