scholarly journals How to Address the Adjuvant Effects of Nanoparticles on the Immune System

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 425 ◽  
Author(s):  
Alexia Feray ◽  
Natacha Szely ◽  
Eléonore Guillet ◽  
Marie Hullo ◽  
François-Xavier Legrand ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Human Monocyte ◽  
Allergic Diseases ◽  
Engineered Nanoparticles ◽  
Phenotypic Analysis ◽  
Adjuvant Effect ◽  
Danger Signals ◽  
Set Up

As the nanotechnology market expands and the prevalence of allergic diseases keeps increasing, the knowledge gap on the capacity of nanomaterials to cause or exacerbate allergic outcomes needs more than ever to be filled. Engineered nanoparticles (NP) could have an adjuvant effect on the immune system as previously demonstrated for particulate air pollution. This effect would be the consequence of the recognition of NP as immune danger signals by dendritic cells (DCs). The aim of this work was to set up an in vitro method to functionally assess this effect using amorphous silica NP as a prototype. Most studies in this field are restricted to the evaluation of DCs maturation, generally of murine origin, through a limited phenotypic analysis. As it is essential to also consider the functional consequences of NP-induced DC altered phenotype on T-cells biology, we developed an allogeneic co-culture model of human monocyte-derived DCs (MoDCs) and CD4+ T-cells. We demonstrated that DC: T-cell ratios were a critical parameter to correctly measure the influence of NP danger signals through allogeneic co-culture. Moreover, to better visualize the effect of NP while minimizing the basal proliferation inherent to the model, we recommend testing three different ratios, preferably after five days of co-culture.

scholarly journals T-cell–intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy

2016 ◽  
Vol 113 (5) ◽  
pp. E568-E576 ◽  
Author(s):  
Jimena Perez-Lloret ◽  
Isobel S. Okoye ◽  
Riccardo Guidi ◽  
Yashaswini Kannan ◽  
Stephanie M. Coomes ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Allergic Diseases ◽  
Treg Cells ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Cytokines And Chemokines ◽  
Th2 Cell

There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αβ+CD4+ T-helper 2 (TH2) cells orchestrate the type-2–driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic TH2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic TH cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081–E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1α)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4gfp+αβ+CD4+ TH2 cells but not in TH1, TH17, or Treg cells. Testing this prediction, we restricted Trim24 deficiency to T cells by using a mixed bone marrow chimera system and found that T-cell–intrinsic Trim24 is essential for HDM-mediated airway allergy and antihelminth immunity. Mechanistically, HDM-elicited Trim24−/− T cells have reduced expression of many TH2 cytokines and chemokines and were predicted to have compromised IL-1–regulated signaling. Following this prediction, we found that Trim24−/− T cells have reduced IL-1 receptor (IL-1R) expression, are refractory to IL-1β–mediated activation in vitro and in vivo, and fail to respond to IL-1β–exacerbated airway allergy. Collectively, these data identify a previously unappreciated Trim24-dependent requirement for IL-1R expression on TH2 cells and an important nonredundant role for T-cell–intrinsic Trim24 in TH2-mediated allergy and antihelminth immunity.

scholarly journals The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Min Sun Shin ◽  
Hong-Jai Park ◽  
Takahiro Maeda ◽  
Hiroshi Nishioka ◽  
Hajime Fujii ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Natural Killer ◽  
Animal Studies ◽  
Lentinula Edodes ◽  
Traditional Medicines ◽  
Immune Mediated ◽  
Health And Disease

Mushrooms have been used for various health conditions for many years by traditional medicines practiced in different regions of the world although the exact effects of mushroom extracts on the immune system are not fully understood. AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia (ECLM) which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through liquid culture. AHCC® is reported to modulate the numbers and functions of immune cells including natural killer (NK) and T cells which play important roles in host defense, suggesting the possible implication of its supplementation in defending the host against infections and malignancies via modulating the immune system. Here, we review in vivo and in vitro effects of AHCC® on NK and T cells of humans and animals in health and disease, providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC®.

Elevated CD54 Expression Renders CD4+ T Cells Susceptible to Natural Killer Cell-Mediated Killing

2019 ◽  
Vol 220 (12) ◽  
pp. 1892-1903 ◽  
Author(s):  
Xi Chen ◽  
Huihui Chen ◽  
Zining Zhang ◽  
Yajing Fu ◽  
Xiaoxu Han ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd4 T Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune Response ◽  
Phenotypic Analysis

Abstract Background Natural killer (NK) cells are an important type of effector cell in the innate immune response, and also have a role in regulation of the adaptive immune response. Several studies have indicated that NK cells may influence CD4+ T cells during HIV infection. Methods In total, 51 HIV-infected individuals and 15 healthy controls participated in this study. We performed the flow cytometry assays and real-time PCR for the phenotypic analysis and the functional assays of NK cell-mediated deletion of CD4+ T cells, phosphorylation of nuclear factor-κB (NF-κB/p65) and the intervention of metformin. Results Here we detected high CD54 expression on CD4+ T cells in HIV-infected individuals, and demonstrate that upregulated CD54 is associated with disease progression in individuals infected with HIV. We also show that CD54 expression leads to the deletion of CD4+ T cells by NK cells in vitro, and that this is modulated by NF-κB/p65 signaling. Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-κB/p65 phosphorylation. Conclusions Our data suggest that further studies to evaluate the potential role of metformin as adjunctive therapy to reconstitute immune function in HIV-infected individuals are warranted.

DC-Based Vaccines Show in-Vitro Activity against Chronic Myeloid Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4276-4276
Author(s):  
Yuen-Fen Tan ◽  
Soon-Keng Cheong ◽  
Chooi-Fun Leong ◽  
SAW Fadhilah
Keyword(s):  
T Cells ◽  
Immune System ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Leukemic Cells ◽  
Gm Csf ◽  
Dc Vaccine ◽  
Hla Dr

Abstract Chronic Myeloid leukemia is a common myeloproliferative disease. Despite recent advances in targeted therapy, only 7–12% of patients achieve molecular remission. Leukemic cells arrange multiple mechanisms to avoid recognition by the immune system. Dendritic cells (DC) are professional antigen presenting cells of the immune system playing a crucial role in the induction of anti-tumor responses. The use of DC is an attractive immunotherapeutic strategy against cancers, especially in minimal residual disease state. In this study, DC vaccine against chronic myeloid leukemia was generated and evaluated in-vitro. Monocytes were isolated and enriched from peripheral blood. These monocytes were subsequently cultured in RPMI medium supplemented with GM-CSF and IL-4 to induce them to become DC. These DC were then co-cultured with tumor lysates obtained from CML cell line in culture medium supplemented with GM-CSF, IL-4 and TNF alpha to become DC-based CML vaccine. The generated DC-based CML vaccines retained their DC morphology, showed strong expression of CD 86 and HLA-DR, and were negative for CD14. Mixed lymphocyte reaction indicated that the generated DC-based CML vaccines were capable of inducing proliferative responses to allogeneic lymphocytes. DC-based CML vaccines were shown to stimulate T cells to express DC-ligands, ie CD28 and CD154, as well as HLA-DR, CD71 and CD 25. In addition, the stimulated T cells were cytotoxic to CML cells used to prepare tumor lysates.

scholarly journals The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1

2001 ◽  
Vol 86 (7) ◽  
pp. 3157-3161
Author(s):  
O. Khorram ◽  
M. Garthwaite ◽  
T. Golos
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Cell Line ◽  
Immune Cell ◽  
Hormone Replacement ◽  
Men And Women

GHRH is a neuropeptide that has also been localized to the immune system. The physiological function of GHRH in the immune system has not been elucidated. This study was conducted to determine whether immune GHRH expression is altered in certain pathological states, such as immune cell tumors, and whether gender, aging, and alterations in the sex steroid milieu influence the expression of this peptide in immune cells. Using double color flow cytometry, GHRH protein was found to be expressed in less than 2% of peripheral blood mononuclear cells (PBMC). Monocytes and B and T cells all expressed GHRH protein, although a greater percentage of T cells compared with B cells and monocytes expressed GHRH (5- to 7-fold). Semiquantitative RT-PCR was used to quantify GHRH messenger ribonucleic acid (mRNA) in PBMC and several immune cell-derived tumors. PBMC and granulocytes expressed low levels of GHRH mRNA with relatively higher levels of expression in monocytes. The tumor cell lines CEMX 174 (B/T cells), HUT 78 (T cells), WIL2-N (B cells), U937 (monocytes/macrophages), and JM 1 (pre-B cell lymphoma) all showed greater expression of GHRH mRNA relative to PBMC. However, two cell lines, CCRF-SB, a B lymphoblastoid cell line, and HL-60, a promyelocytic cell line, expressed GHRH mRNA at similar levels as PBMC. A significant decrease in the percentage of lymphocytes (CD45+ cells) expressing GHRH protein was found in age-advanced men and women compared with young men and women. This decline was noted in B cells (CD20+) and monocytes (CD14+), but not in T cells (CD3+). GHRH mRNA expression in PBMC derived from postmenopausal women was lower than that from premenopausal women. However, no differences in PBMC GHRH mRNA expression were found in young and old men. Although in older men there were fewer peripheral lymphocytes that express GHRH protein, these cells secreted significantly more GHRH in vitro than cells from postmenopausal women with no hormone replacement therapy (HRT), but similar levels as cells from women receiving HRT. PBMC from women receiving HRT secreted more GHRH in vitro than cells from women receiving no hormone replacement. This study demonstrates that the expression of immune GHRH is dynamic, and therefore likely to be regulated. Increased expression of GHRH in certain immune tumors suggests that GHRH may be mitogenic under certain conditions and therefore play a role in the pathogenesis of select immune cell tumors. Collectively, these results suggest a role for GHRH as a local immune modulator and in the pathophysiology of immunosenescence and immune cell tumors.

Role of T cells in the adjuvant effect ofbacillus firmus on the immune system of mice: Intranasal and intratracheal immunization study with ovalbumin

2003 ◽  
Vol 48 (3) ◽  
pp. 427-434 ◽  
Author(s):  
P. Mlčková ◽  
D. Čechová ◽  
L. Marušková ◽  
P. Chalupná ◽  
O. Novotná ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Adjuvant Effect ◽  
Immunization Study

scholarly journals Immunoregulatory Natural Killer Cells Suppress Autoimmunity by Down-Regulating Antigen-Specific CD8+ T Cells in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4367-4379 ◽  
Author(s):  
Margret Ehlers ◽  
Claudia Papewalis ◽  
Wiebke Stenzel ◽  
Benedikt Jacobs ◽  
Klaus L. Meyer ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Lysis Activity ◽  
Nonobese Diabetic Mice

Natural killer (NK) cells belong to the innate immune system. Besides their role in antitumor immunity, NK cells also regulate the activity of other cells of the immune system, including dendritic cells, macrophages, and T cells, and may, therefore, be involved in autoimmune processes. The aim of the present study was to clarify the role of NK cells within this context. Using two mouse models for type 1 diabetes mellitus, a new subset of NK cells with regulatory function was identified. These cells were generated from conventional NK cells by incubation with IL-18 and are characterized by the expression of the surface markers CD117 (also known as c-Kit, stem cell factor receptor) and programmed death (PD)-ligand 1. In vitro analyses demonstrated a direct lysis activity of IL-18-stimulated NK cells against activated insulin-specific CD8+ T cells in a PD-1/PD-ligand 1-dependent manner. Flow cytometry analyses revealed a large increase of splenic and lymphatic NK1.1+/c-Kit+ NK cells in nonobese diabetic mice at 8 wk of age, the time point of acceleration of adaptive cytotoxic immunity. Adoptive transfer of unstimulated and IL-18-stimulated NK cells into streptozotocin-treated mice led to a delayed diabetes development and partial disease prevention in the group treated with IL-18-stimulated NK cells. Consistent with these data, mild diabetes was associated with increased numbers of NK1.1+/c-Kit+ NK cells within the islets. Our results demonstrate a direct link between innate and adaptive immunity in autoimmunity with newly identified immunoregulatory NK cells displaying a potential role as immunosuppressors.

scholarly journals Anti–IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived dendritic cell maturation or alloreactive T-cell responses

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5340-5343 ◽  
Author(s):  
Brian C. Betts ◽  
Erin T. St Angelo ◽  
Michael Kennedy ◽  
James W. Young
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Human Monocyte ◽  
T Cell Proliferation ◽  
Dendritic Cell Activation ◽  
Alloreactive T Cell

Abstract Significant comorbidites and lethality complicate GVHD and its treatment. Targeting the cytokine milieu may improve GVHD control; and IL6 is an attractive candidate, given its role in dendritic cell activation and T-cell differentiation. Tocilizumab is a humanized mAb to IL6-receptor-α (IL6R-α), which is Food and Drug Administration–approved for treatment of rheumatoid arthritis. Mouse transplant models have demonstrated that IL6 blockade also improves GVHD scores and survival. Definitive immunologic effects of IL6 inhibition have not emerged given inconsistent alterations in regulatory T cells (Tregs) and suppression of T-cell proliferation. Despite on-target suppression of IL6R-α signaling in human monocyte-derived dendritic cells (moDCs) and T cells, our data show no effect on moDC maturation/activation, alloreactive T-cell proliferation, Treg expansion, or allogeneic Th1/Th17 responses in vitro. These findings merit attention in any clinical trials of tocilizumab for GVHD prevention or treatment and provide a rationale for evaluating more specific inhibitors of downstream JAK2/STAT3 signaling as well.

scholarly journals Pengaruh ekstrak etanol daun ungu (EEDU) Graptophyllum pictum L. Griff terhadap aktivitas fagositosis monosit yang dipapar Candida albicans

DENTA ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 45
Author(s):  
Atik Kurniawati
Keyword(s):  
Candida Albicans ◽  
Immune System ◽  
Phagocytic Activity ◽  
Ethanol Extract ◽  
Human Monocyte ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group

<p class="Standard"><strong><em>Background</em></strong><em>:<strong> </strong>Candidiasis is one of oral infectious disease caused by Candida albicans.The role of C. albicans as pathogen opportunistic in oral infection can affected by immune system. Phagocytosis has contributed in immune system against C. albicans infection, which is the role of monocytes. Grapthophyllum L. Griff has been proved to increase macrophage’s phagocytic activity, but the effect of violet leaves ethanol extract (EEDU) to increase monocyte’s phagocytic activity on C. albicans is unknown. <strong>Objectives</strong>:<strong> </strong>To determine the effect of violet leaves extract on monocyte’s phagocytic activity on C. albicans. <strong>Methods</strong>: This research was acted in vitro on human monocyte cell culture. There was 5 groups: negative control group, positive control group (incubated in Isoprinosine) and treatment groups was incubated in EEDU 2,5%, 5%, 10%. The percentage of activated monocytes was counted. <strong>Result</strong>: The result showed that incubation of EEDU 2,5%, 5% and 10% could increase monocyte’s phagocytic activity significantly (p&lt;0,05) compared to control groups. The number of monocyte’s phagocytosis on C. albicans incubated with EEDU 2,5%, 5% and 10% is 65%, 60,5%, and 58,75%. The optimal concentration of EEDU to increase monocyte’s phagocytic activity was 2,5%. <strong>Conclusion</strong>: The study showed that EEDU can increase monocyte’s phagocytic activity on C. albicans.</em></p><p class="Standard"><em>            </em></p><p class="Standard"><strong><em>Keywords</em></strong><em>:Ethanol extract of Graptophyllum pictum L. Griff  leaves, Monocyte’s Phagocytic Activity, Candida albicans </em></p>

scholarly journals CRISPR/Cas9-mediated TGFβRII disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Khadijeh Alishah ◽  
Matthias Birtel ◽  
Elham Masoumi ◽  
Leila Jafarzadeh ◽  
Hamid Reza Mirzaee ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Solid Tumors ◽  
Target Cells ◽  
Cell Functions ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract Background CAR T-cell therapy has been recently unveiled as one of the most promising cancer therapies in hematological malignancies. However, solid tumors mount a profound line of defense to escape immunosurveillance by CAR T-cells. Among them, cytokines with an inhibitory impact on the immune system such as IL-10 and TGFβ are of great importance: TGFβ is a pleiotropic cytokine, which potently suppresses the immune system and is secreted by a couple of TME resident and tumor cells. Methods In this study, we hypothesized that knocking out the TGFβ receptor II gene, could improve CAR T-cell functions in vitro and in vivo. Hereby, we used the CRISPR/Cas9 system, to knockout the TGFβRII gene in T-cells and could monitor the efficient gene knock out by genome analysis techniques. Next, Mesothelin or Claudin 6 specific CAR constructs were overexpressed via IVT-RNA electroporation or retroviral transduction and the poly-functionality of these TGFβRII KO CAR T-cells in terms of proliferation, cytokine secretion and cytotoxicity were assessed and compared with parental CAR T-cells. Results Our experiments demonstrated that TGFβRII KO CAR T-cells fully retained their capabilities in killing tumor antigen positive target cells and more intriguingly, could resist the anti-proliferative effect of exogenous TGFβ in vitro outperforming wild type CAR T-cells. Noteworthy, no antigen or growth factor-independent proliferation of these TGFβRII KO CAR T-cells has been recorded. TGFβRII KO CAR T-cells also resisted the suppressive effect of induced regulatory T-cells in vitro to a larger extent. Repetitive antigen stimulation demonstrated that these TGFβRII KO CAR T-cells will experience less activation induced exhaustion in comparison to the WT counterpart. Conclusion The TGFβRII KO approach may become an indispensable tool in immunotherapy of solid tumors, as it may surmount one of the key negative regulatory signaling pathways in T-cells.

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