scholarly journals BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro

Immunology ◽  
2007 ◽  
Vol 121 (2) ◽  
pp. 276-282 ◽  
Author(s):  
Jeppe Madura Larsen ◽  
Christine Stabell Benn ◽  
Yvonne Fillie ◽  
Desiree van der Kleij ◽  
Peter Aaby ◽  
...  
Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1021
Author(s):  
Ho-Jae Lee ◽  
Joon Seok Park ◽  
Hyun Jung Yoo ◽  
Hae Min Lee ◽  
Byung Cheon Lee ◽  
...  

Immune activation associates with the intracellular generation of reactive oxygen species (ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidence shows that ROS-mediated signal transduction can be regulated by selenoproteins such as methionine sulfoxide reductase B1 (MsrB1). However, how the selenoprotein shapes immunity remains poorly understood. Here, we demonstrated that MsrB1 plays a crucial role in the ability of dendritic cells (DCs) to provide the antigen presentation and costimulation that are needed for cluster of differentiation antigen four (CD4) T-cell priming in mice. We found that MsrB1 regulated signal transducer and activator of transcription-6 (STAT6) phosphorylation in DCs. Moreover, both in vitro and in vivo, MsrB1 potentiated the lipopolysaccharide (LPS)-induced Interleukin-12 (IL-12) production by DCs and drove T-helper 1 (Th1) differentiation after immunization. We propose that MsrB1 activates the STAT6 pathway in DCs, thereby inducing the DC maturation and IL-12 production that promotes Th1 differentiation. Additionally, we showed that MsrB1 promoted follicular helper T-cell (Tfh) differentiation when mice were immunized with sheep red blood cells. This study unveils as yet unappreciated roles of the MsrB1 selenoprotein in the innate control of adaptive immunity. Targeting MsrB1 may have therapeutic potential in terms of controlling immune reactions.


Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 523-527 ◽  
Author(s):  
Reinhard Dummer ◽  
Udo Döbbeling ◽  
Ralf Geertsen ◽  
Jörg Willers ◽  
Günter Burg ◽  
...  

Abstract Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of lymphoproliferative disorders that are characterized by an accumulation of T-lymphocytes in the skin and occasionally in blood known as Sézary syndrome (SS). In most cases the dominant clone displays T-helper 2 cytokines. Because IFN-γ is a natural inhibitor of T-helper 2 cells and IFN-α is frequently used in CTCL, the impact of IFNs on SS-derived purified clonal T-helper 2 cells was studied using anti-Vβ antibodies. Moreover, IFNs are known to mediate virus resistance in normal cells. The isolated clonal CD4+ cells, but not the nonclonal CD4+ cells, appeared resistant to IFN-γ and IFN-α stimulation in terms of human leukocyte antigen up-regulation and MxA induction caused in part by alterations in Stat-1 molecule mRNA and IFNγR1 mRNA transcription. The IFN resistance of the patient-derived clonal cells was then targeted by vesicular stomatitis virus infection after IFN-α priming, resulting in selective viral replication in clonal cells. In contrast, nonclonal cells of the same patient showed IFN-dependent MxA expression, which is a major mediator protein of viral protection. The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis. Interferon signaling deficiencies can be targeted for purging patients' cells in vitro. Furthermore, this approach may allow specific molecular interventions, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Rufine Fachinan ◽  
Adnette Fagninou ◽  
Magloire Pandoua Nekoua ◽  
Abdou Madjid Amoussa ◽  
Marius Adjagba ◽  
...  

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN-γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections.


2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Mauricio Llaguno ◽  
Marcos Vinicius da Silva ◽  
Lara Rocha Batista ◽  
Djalma Alexandre Alves da Silva ◽  
Rodrigo Cunha de Sousa ◽  
...  

ABSTRACT The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25− and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.


2001 ◽  
Vol 75 (18) ◽  
pp. 8649-8659 ◽  
Author(s):  
Ann Leen ◽  
Pauline Meij ◽  
Irina Redchenko ◽  
Jaap Middeldorp ◽  
Elisabeth Bloemena ◽  
...  

ABSTRACT Human CD4+ T-helper 1 cell responses to Epstein-Barr virus (EBV) infection are likely to be important in the maintenance of virus-specific CD8+ memory and/or as antiviral effectors in their own right. The present work has used overlapping peptides as stimulators of gamma interferon release (i) to identify CD4+ epitopes within four EBV latent-cycle proteins, i.e., the nuclear antigens EBNA1 and EBNA3C and the latent membrane proteins LMP1 and LMP2, and (ii) to determine the frequency and magnitude of memory responses to these proteins in healthy virus carriers. Responses to EBNA1 and EBNA3C epitopes were detected in the majority of donors, and in the case of EBNA1, their antigen specificity was confirmed by in vitro reactivation and cloning of CD4+ T cells using protein-loaded dendritic cell stimulators. By contrast, responses to LMP1 and LMP2 epitopes were seen much less frequently. EBV latent-cycle proteins therefore display a marked hierarchy of immunodominance for CD4+ T-helper 1 cells (EBNA1, EBNA3C ≫ LMP1, LMP2) which is different from that identified for the same proteins with respect to CD8+-T-cell responses (EBNA3C > EBNA1 > LMP2 ≫ LMP1). Furthermore, the range of CD4+ memory T-cell frequencies in peripheral blood of healthy virus carriers was noticeably lower and narrower than the corresponding range of latent antigen-specific CD8+-T-cell frequencies.


2011 ◽  
Vol 1 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Jennifer K. Mulligan ◽  
Ryan M. Mulligan ◽  
Carl Atkinson ◽  
Rodney J. Schlosser

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