scholarly journals Interleukin 35: an overview

2020 ◽  
Author(s):  
Natalia Zdanowska ◽  
Agnieszka Barbara Owczarczyk-Saczonek ◽  
Wojciech Zdanowski ◽  
Waldemar Juliusz Placek
Keyword(s):  
T Cells ◽  
Cardiovascular Diseases ◽  
Cd8 T Cells ◽  
Current Knowledge ◽  
Γδ T Cells ◽  
Immune Dysregulation ◽  
Regulatory B Cells ◽  
Forkhead Box ◽  
Neurologic Disorders ◽  
Antigen Presenting

Introduction: Interleukin 35 (IL-35) has recently been characterized as a cytokine connected with the IL-12 group. The secretion of IL-35 was described in forkhead box protein 3 (Foxp3) + regulatory T cells (Tregs), peripheral γδ T cells, CD8+ T cells, placental trophoblasts, antigen-presenting cells (APCs) and regulatory B cells (Breg). Aim: The aim of this paper is to systematize current knowledge about IL-35 production and discuss its impact on the pathophysiology and outcome of various diseases. Material and methods: Literature review was conducted. Results and discussion: IL-35 plays a pivotal role in the immune dysregulation in the pathogenesis of cardiovascular diseases including atherosclerosis, psychiatric and neurologic disorders, cancer, allergic and autoimmune diseases and psoriasis, inducing the expression of Treg-related cytokines and inhibiting the expression of Th1- and Th17-related cytokines.

Presentation of Epstein Barr Virus (EBV) Epitopes by Activated Human γδ T Cells Induces Peptide-Specific Cytolytic CD8+ T Cell Expansion.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1738-1738 ◽  
Author(s):  
Silke Landmeier ◽  
Bianca Altvater ◽  
Sibylle Pscherer ◽  
Lena Varnholt ◽  
Catherine M. Bollard ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Epstein Barr Virus ◽  
Γδ T Cells ◽  
Lytic Cycle ◽  
Barr Virus ◽  
Hla Dr ◽  
Epstein Barr ◽  
Antigen Presenting

Abstract Efficient antigen presentation is an important prerequisite for the induction of T cell mediated immunity against viral and tumor antigens. The functional heterogeneity, limited availability and poor expansion of dendritic cells (DC) has motivated a search for alternative sources of antigen-presenting cells (APC). Bisphosphonate-activated human γδ T cells were shown to function as APC by inducing primary T cell responses to allogeneic and microbial antigens. Here, we extended these observations by investigating the capacity of activated γδ T cells to present Epstein Barr virus lytic cycle and latency antigens in a peptide-specific manner and induce expansion of fully functional, virus-specific cytotoxic αβ T cells. Peripheral blood-derived γδ T cells were expanded from three individual healthy donors by stimulation with the aminobisphosphonate zoledronic acid (1 μg/ml) in the presence of rhIL-2 (100 U/ml) and rhIL-15 (10 ng/ml). Under these conditions, γδ T cells (Vγ9+Vδ2+) acquired a phenotype characteristic for APC, including upregulation of HLA-DR as well as the costimulatory ligands CD80, CD83, CD86, CD40, and 4-1BBL (CDw137L). Whereas expression of most markers decreased after peak levels were reached on day 5, CD86 and HLA-DR remained upregulated on >80% of the cells for prolonged culture periods of >14 days. We next assessed the APC function of activated γδ T cells by testing their ability to stimulate expansion of antigen-specific cytotoxic T cells in vitro. Autologous peripheral blood lymphocytes (PBMC) were incubated with activated γδ T cells pulsed with the HLA-B8-restricted epitope of the EBV lytic cycle antigen BZLF1 (RAKFKQLL). We demonstrated selective expansion of RAK-pentamer-specific CD3+ CD8+ T cells to a mean of 15% (range 6–24%) on day 10. BZLF-1 represents a highly immunogenic virus antigen, whereas the EBV latency-associated antigen LMP-2a is less T cell-stimulatory and, due to its expression on Hodgkin′s lymphoma cells, is an important target for tumor-specific immune therapy. Stimulation of PBMC with γδ T cells pulsed with the HLA-A2-restricted LMP2a epitope FLYALALLL also resulted in a substantial increase of pentamer-reactive T cells to a mean of 3.5% (1.4–5.5%), which was comparable to the increase obtained when peptide-loaded autologous DC were used (mean of 3.5%; range 1.2–5.7%). γδ T cell stimulation in the absence of peptide failed to induce specific T cell expansion (mean of 0.1%; 0.03–0.15%). CD8+ T cells expanded against EBV-peptide-pulsed activated γδ T cells functionally interacted with peptide-loaded autologous DC or lymphoblastoid cell lines (LCL), as demonstrated by efficient and specific MHC class I-restricted cytolysis of 41–65% at an effector-target ratio of 40:1. Peptide-specific cytotoxic T cell functionality was comparable to that obtained with T cells expanded in the presence of pulsed autologous DC from the same donors. In summary, bisphosphonate-activated γδ T cells are potent antigen-presenting cells for reproducible expansion of disease antigen-specific CTL. Thus, they represent a novel source of highly efficient professional APC for antigen-specific immunotherapy of viral or malignant disease.

scholarly journals DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors

2008 ◽  
Vol 205 (13) ◽  
pp. 2965-2973 ◽  
Author(s):  
Susan Gilfillan ◽  
Christopher J. Chan ◽  
Marina Cella ◽  
Nicole M. Haynes ◽  
Aaron S. Rapaport ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Adhesion Molecules ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Antigen Presenting

Natural killer (NK) cells and CD8 T cells require adhesion molecules for migration, activation, expansion, differentiation, and effector functions. DNAX accessory molecule 1 (DNAM-1), an adhesion molecule belonging to the immunoglobulin superfamily, promotes many of these functions in vitro. However, because NK cells and CD8 T cells express multiple adhesion molecules, it is unclear whether DNAM-1 has a unique function or is effectively redundant in vivo. To address this question, we generated mice lacking DNAM-1 and evaluated DNAM-1–deficient CD8 T cell and NK cell function in vitro and in vivo. Our results demonstrate that CD8 T cells require DNAM-1 for co-stimulation when recognizing antigen presented by nonprofessional antigen-presenting cells; in contrast, DNAM-1 is dispensable when dendritic cells present the antigen. Similarly, NK cells require DNAM-1 for the elimination of tumor cells that are comparatively resistant to NK cell–mediated cytotoxicity caused by the paucity of other NK cell–activating ligands. We conclude that DNAM-1 serves to extend the range of target cells that can activate CD8 T cell and NK cells and, hence, may be essential for immunosurveillance against tumors and/or viruses that evade recognition by other activating or accessory molecules.

scholarly journals Development of an IL-15–autocrine CD8 T-cell leukemia in IL-15–transgenic mice requires the cis expression of IL-15Rα

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 4032-4040 ◽  
Author(s):  
Noriko Sato ◽  
Helen Sabzevari ◽  
Song Fu ◽  
Wei Ju ◽  
Michael N. Petrus ◽  
...  
Keyword(s):  
T Cells ◽  
Transgenic Mice ◽  
Cd8 T Cells ◽  
Constitutive Expression ◽  
Γδ T Cells ◽  
Selective Advantage ◽  
Intraepithelial Lymphocytes ◽  
Leukemic Transformation ◽  
Nk T Cells ◽  
Growth Promoting

AbstractIL-15 has growth-promoting effects on select lymphoid subsets, including natural killer (NK) cells, NK T cells, intraepithelial lymphocytes (IELs), CD8 T cells, and γδ-T cells. Constitutive expression of murine IL-15 in IL-15–transgenic mice was reported to cause T-NK leukemia. We investigated whether IL-15 expression is sufficient for leukemic transformation using a human IL-15–transgenic (IL-15Tg) mouse model. We noted that 100% of the mice observed over a 2-year period (n > 150) developed fatal expansions of CD8 T cells with NK markers, and determined that these cells expressed IL-15 receptor alpha (IL-15Rα). The expression of IL-15Rα on CD8 T cells appears to be required for uncontrolled aggressive lymphoproliferation, because none of the IL-15Rα−/−–IL-15Tg mice that we followed for more than 2 years developed the fatal disease despite controlled expansion of CD8 T cells. In addition, in contrast to IL-15Tg mice, in which leukemia-like CD8 T cells expressed IL-15Rα persistently, acutely activated normal CD8 T cells only transiently expressed IL-15Rα. Inhibition of DNA methylation enabled sustained IL-15Rα expression induced by activation. We present a scenario for IL-15Tg mice in which CD8 T cells that acquire constitutive persistent IL-15Rα expression are at a selective advantage and become founder cells, outgrow other lymphocytes, and lead to the establishment of a leukemia-like condition.

scholarly journals 714 Selective expansion of antigen-specific CD8 T cells with engineered antigen presenting exosome

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A743-A743
Author(s):  
Tomoyoshi Yamano ◽  
Xiabing Lyu ◽  
Rikinari Hanayama
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Costimulatory Molecule ◽  
Animal Experiments ◽  
Surface Proteins ◽  
Hek293 Cells ◽  
Target Cells ◽  
Single Chain ◽  
Antigen Presenting

BackgroundExosomes are vesicular granules of about 100 nm and are secreted by many types of cells. Exosomes contain various proteins, lipids, and RNAs that are transported to target cells which induce functional and physiological changes. Exosomes are promising nano-vesicles for clinical application, owing to their high biocompatibility, low immunogenicity, and high drug delivery efficacy. Recent studies have demonstrated that exosomes from tumor cells or antigen presenting cells (APCs) regulate immune responses. Tumor derived exosomes express PD-L1 on their surface and suppress tumor immunity systemically. On the other hand, mature dendritic cells derived exosomes exert immune activation, and tumor immunotherapy using DCs exosome has been developed. However, few studies have been found to exert a significant effect on cancer treatment, may be because of low expression of costimulatory molecules and lack of cytokines on DCs derived exosomes.MethodsIt has been demonstrated that GFP can be conveyed into exosomes by conjugating GFP with tetraspanins, exosome-specific surface proteins. First, we generated a tetraspanin fusion protein with a single-chain MHCI trimer (scMHCI). IL-2 is inserted on the second extracellular loop of CD81, allowing robust and functional expression of IL-2 on the exosome. We collected exosomes from HEK293 cells culture, which stably express scMHCI-CD81-IL2 and CD80-MFGE8, and used as Antigen-presenting exosome(AP-Exo).ResultsAP-Exo expresses high expression of MHCI-peptide complex, costimulatory molecule, and cytokine, activating cognate CD8 T cells as dendritic cells do. AP-Exo selectively delivered co-stimulation and IL-2 to antigen-specific CD8 T cells, resulting in a massive expansion of antigen-specific CD8 T cells without severe adverse effects in mice. AP-Exo can expand endogenous tumor-specific CD8 T cells and induce the potent anti-tumor effect.ConclusionsOur strategy for building engineered exosomes that work like APCs might develop novel methods for cancer immunotherapy.Ethics ApprovalAll mice were housed in a specific pathogen-free facility, and all animal experiments were performed according to a protocol approved by Kanazawa University, Kanazawa, Japan.

scholarly journals Human Dendritic Cells: Ontogeny and Their Subsets in Health and Disease

2018 ◽  
Vol 6 (4) ◽  
pp. 88 ◽  
Author(s):  
Sandra Solano-Gálvez ◽  
Sonia Tovar-Torres ◽  
María Tron-Gómez ◽  
Ariane Weiser-Smeke ◽  
Diego Álvarez-Hernández ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Current Knowledge ◽  
Lymphoid Organ ◽  
Heterogeneous Population ◽  
Health And Disease ◽  
Human Dendritic Cells ◽  
Activation Status

Dendritic cells (DCs) are a type of cells derived from bone marrow that represent 1% or less of the total hematopoietic cells of any lymphoid organ or of the total cell count of the blood or epithelia. Dendritic cells comprise a heterogeneous population of cells localized in different tissues where they act as sentinels continuously capturing antigens to present them to T cells. Dendritic cells are uniquely capable of attracting and activating naïve CD4+ and CD8+ T cells to initiate and modulate primary immune responses. They have the ability to coordinate tolerance or immunity depending on their activation status, which is why they are also considered as the orchestrating cells of the immune response. The purpose of this review is to provide a general overview of the current knowledge on ontogeny and subsets of human dendritic cells as well as their function and different biological roles.

Antigens and Antigen-Presenting Molecules for γδ T Cells

1991 ◽  
pp. 229-234 ◽  
Author(s):  
H. Band ◽  
St. A. Porcelli ◽  
G. Panchamoorthy ◽  
J. Mclean ◽  
C. T. Morita ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Antigen Presenting

Point mutants of forkhead box P3 that cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked have diverse abilities to reprogram T cells into regulatory T cells

2010 ◽  
Vol 126 (6) ◽  
pp. 1242-1251 ◽  
Author(s):  
Alicia N. McMurchy ◽  
Jana Gillies ◽  
Sarah E. Allan ◽  
Laura Passerini ◽  
Eleonora Gambineri ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Dysregulation ◽  
Forkhead Box P3 ◽  
Forkhead Box

scholarly journals Complete differentiation of CD8+ T cells activated locally within the transplanted liver

2006 ◽  
Vol 203 (2) ◽  
pp. 437-447 ◽  
Author(s):  
Ingo Klein ◽  
Ian Nicholas Crispe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Underlying Mechanism ◽  
Color Flow ◽  
Antigen Presenting ◽  
Transplantation Model

The transplanted liver elicits systemic tolerance, and the underlying mechanism may also account for the persistence of liver infections, such as malaria and viral hepatitis. These phenomena have led to the hypothesis that antigen presentation within the liver is abortive, leading to T cell tolerance or apoptosis. Here we test this hypothesis in an optimized orthotopic liver transplantation model. In direct contradiction to this model, the liver itself induces full CD8+ T cell activation and differentiation. The effects of microchimerism were neutralized by bone marrow transplantation in the liver donor, and the lack of liver-derived antigen-presenting cells was documented by eight-color flow cytometry and by sensitive functional assays. We conclude that local antigen presentation cannot explain liver tolerance. On the contrary, the liver may be an excellent priming site for naive CD8+ T cells.

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