scholarly journals IN VITRO ACTIVATION OF CELLULAR IMMUNE RESPONSE TO GROSS VIRUS-INDUCED LYMPHOMA

1972 ◽  
Vol 136 (5) ◽  
pp. 969-983 ◽  
Author(s):  
Manuel Ortiz de Landazuri ◽  
Ronald B. Herberman
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Surface Characteristics ◽  
Immune Serum ◽  
Lymphoid Cells ◽  
Rat Serum ◽  
In Vitro Incubation ◽  
Central Inhibition

Spleen cells from W/Fu rats 40 days or more after immunization with a syngeneic Gross virus-induced leukemia were unreactive in direct cytotoxic assays. Incubation of these immune cells at 37°C for 12 hr or longer, in the absence of antigen, resulted in the appearance of specific cytotoxic reactivity. Other lymphoid cells from the immune rats also were activated upon in vitro incubation, but to a lesser extent. Experiments were performed to define the necessary conditions and the mechanism for the in vitro incubation. Activation was temperature dependent, occurring at 37°C but not at 4°C. Immune serum suppressed the activation, but normal rat serum also had some inhibitory activity. Passage of immune cells through a nylon column, before preincubation, prevented activation. In contrast, exposure to nylon after preincubation did not remove cytotoxic reactivity. These findings demonstrate the reversal of a central inhibition of immune cell activity. The explanations offered for this phenomenon included change in surface characteristics of the immune cells during in vitro incubation, and the possible need for an adherent helper cell.

scholarly journals Characterization of the Role of Regulatory T Cells (Tregs) in Inducing Progression of Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 502-502 ◽  
Author(s):  
Yawara Kawano ◽  
Michele Moschetta ◽  
Katsutoshi Kokubun ◽  
Pavlo Lukyanchykov ◽  
Esilida Sula Karreci ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rna Sequencing ◽  
Mouse Models ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Treg Depletion

Abstract Introduction. Growing evidence suggests that immune cells that reside within the tumor microenvironment are dysregulated and functionally impaired, leading to defective anti-tumor immunity of the host. One of the major immunosuppressive mechanisms during tumor progression is expansion of regulatory immune cells. Here, we analyzed the immune cells within the bone marrow (BM) and the peripheral blood (PB) of 2 immunocompetent multiple myeloma (MM) mouse models. We next studied the role of regulatory T cells (Tregs) in MM pathogenesis. Materials and methods. To study the immune cell populations of the BM and PB, we used two immuncompetent mouse models and transplanted VK*MYC cells or 5TGM1 cells into C57BL/6 and C57BL/Kalwrij mice respectively. The immune cell populations and checkpoint receptor expressions were analyzed by CyTOF mass cytometer or flow-cytometry. Treg induction assay was performed in vitro to study the mechanism of Treg increase in the BM of myeloma injected mice. CD4+ CD25- cells were obtained from C57BL/Kalwrij mice and were co-cultured with 5TGM1 cells or B cells from C57BL/Kalwrij mice in vitro. Treg induction was compared by flow-cytometry. Transplantable VK*MYC cells were injected into "depletion of regulatory T cell" (DEREG) mice, which expresses a simian diphtheria toxin (DT) receptor-enhanced GFP fusion protein under the control of the FOXP3 gene locus, or their wild type littermates. DT injection into these mice leads to depletion of Tregs as previously described (J Exp Med. 2007; 204: 57-63). DT was given once every week for a total 3 times i.p to the DEREG mice or the littermate controls to specifically deplete Tregs and to study the role of Tregs during MM progression. Tregs (CD4+ FOXP3-GFP+ cells) were sorted from VK*MYC injected mice or non-injected DEREG mice BM using FACSAria cell sorter. Cells isolated were subjected to RNA sequencing. Gene Set Enrichment Analysis (GSEA) was performed to define differences in molecular signatures between MM-associated and normal Tregs. Results. The Treg proportion was significantly increased within the CD4+ T cells in the BM of myeloma cell injected mice from the early stage of disease compared to control mice, while in the PB, the increase was observed only at the late stages of disease progression. The effector T cell (Teff)/Treg ratio was significantly decreased in the BM at the end-stage myeloma bearing mice (P<0.01). Checkpoint related molecules (PD-1, LAG-3 and Tim-3) on Tregs and Teffs were up-regulated at the protein level in the BM of myeloma injected mice compared to control (P<0.01). These data indicate the activation of Tregs and decrease of Teff activity, leading to suppression of anti-myeloma T cell activity in the MM BM. Under in vitro co-culture conditions, 5TGM1 cells induced a significant increase in the number of Tregs from non-Treg CD4+ T cells compared to controls (P<0.01). 5TGM1 cell-induced Tregs presented with enhanced ki-67 expression, thus suggesting the ability of MM cells to induce Treg proliferation. Additionally, the trans-well co-culture experiment showed that the major mechanism for Treg induction by 5TGM1 was by direct contact with T cells rather than secreting factors. Significant increase in survival was observed in the VK*MYC injected DEREG mice under Treg depletion compared to the DEREG mice without Treg depletion and wild type littermates under DT treatment (P<0.001). The Treg depleted DEREG mice were accompanied with an increase of Teffs (P<0.01), indicating recovery of anti-myeloma T cell activity. RNA sequencing of BM Tregs from VK*MYC injected mice showed increased expression of immune checkpoint related molecules and increased Treg effector molecules (IL-10, Granzyme B) compared to BM Tregs from control mice, indicating a more functionally active phenotype of VK*MYC associated Tregs. GSEA showed an enrichment of genes involved in type-1 interferon signaling in VK*MYC associated Tregs. Conclusions. We used 2 immunocompetent MM mouse models to study the characterization and significance of Tregs in MM progression. CyTOF analysis and RNA sequencing data indicated Treg activation in the MM BM microenvironment. The Treg in vivo depletion experiment showed that Tregs have a significant role in MM progression. These data indicate that immunotherapy targeting Tregs may represent a novel therapeutic strategy for MM. Studies are ongoing to understand the roles of Tregs in human MM patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals How Changes in the Nutritional Landscape Shape Gut Immunometabolism

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 823
Author(s):  
Jian Tan ◽  
Duan Ni ◽  
Rosilene V. Ribeiro ◽  
Gabriela V. Pinget ◽  
Laurence Macia
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Immune Cell ◽  
Food Additives ◽  
Cell Activity ◽  
Inflammatory Cells ◽  
Therapeutic Approaches ◽  
Food Antigens ◽  
And Function ◽  
Micro Organisms

Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.

scholarly journals In Vitro Evaluation of CD276-CAR NK-92 Functionality, Migration and Invasion Potential in the Presence of Immune Inhibitory Factors of the Tumor Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1020
Author(s):  
Stefan Grote ◽  
Guillermo Ureña-Bailén ◽  
Kenneth Chun-Ho Chan ◽  
Caroline Baden ◽  
Markus Mezger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Immune Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Migration And Invasion ◽  
Cellular Immunotherapy ◽  
Knock Out ◽  
Immunosuppressive Tumor Microenvironment

Background: Melanoma is the most lethal of all skin-related cancers with incidences continuously rising. Novel therapeutic approaches are urgently needed, especially for the treatment of metastasizing or therapy-resistant melanoma. CAR-modified immune cells have shown excellent results in treating hematological malignancies and might represent a new treatment strategy for refractory melanoma. However, solid tumors pose some obstacles for cellular immunotherapy, including the identification of tumor-specific target antigens, insufficient homing and infiltration of immune cells as well as immune cell dysfunction in the immunosuppressive tumor microenvironment (TME). Methods: In order to investigate whether CAR NK cell-based immunotherapy can overcome the obstacles posed by the TME in melanoma, we generated CAR NK-92 cells targeting CD276 (B7-H3) which is abundantly expressed in solid tumors, including melanoma, and tested their effectivity in vitro in the presence of low pH, hypoxia and other known factors of the TME influencing anti-tumor responses. Moreover, the CRISPR/Cas9-induced disruption of the inhibitory receptor NKG2A was assessed for its potential enhancement of NK-92-mediated anti-tumor activity. Results: CD276-CAR NK-92 cells induced specific cytolysis of melanoma cell lines while being able to overcome a variety of the immunosuppressive effects normally exerted by the TME. NKG2A knock-out did not further improve CAR NK-92 cell-mediated cytotoxicity. Conclusions: The strong cytotoxic effect of a CD276-specific CAR in combination with an “off-the-shelf” NK-92 cell line not being impaired by some of the most prominent negative factors of the TME make CD276-CAR NK-92 cells a promising cellular product for the treatment of melanoma and beyond.

Exercise-induced immunodepression– plasma glutamine is not the link

2002 ◽  
Vol 93 (3) ◽  
pp. 813-822 ◽  
Author(s):  
Natalie Hiscock ◽  
Bente Klarlund Pedersen
Keyword(s):  
Immune Cells ◽  
Killer Cell ◽  
Cell Activity ◽  
Exhaustive Exercise ◽  
Glutamine Supplementation ◽  
Strenuous Exercise ◽  
Glutamine Concentration ◽  
Killer Cell Activity ◽  
Exercise Induced

The amino acid glutamine is known to be important for the function of some immune cells in vitro. It has been proposed that the decrease in plasma glutamine concentration in relation to catabolic conditions, including prolonged, exhaustive exercise, results in a lack of glutamine for these cells and may be responsible for the transient immunodepression commonly observed after acute, exhaustive exercise. It has been unclear, however, whether the magnitude of the observed decrease in plasma glutamine concentration would be great enough to compromise the function of immune cells. In fact, intracellular glutamine concentration may not be compromised when plasma levels are decreased postexercise. In addition, a number of recent intervention studies with glutamine feeding demonstrate that, although the plasma concentration of glutamine is kept constant during and after acute, strenuous exercise, glutamine supplementation does not abolish the postexercise decrease in in vitro cellular immunity, including low lymphocyte number, impaired lymphocyte proliferation, impaired natural killer and lymphokine-activated killer cell activity, as well as low production rate and concentration of salivary IgA. It is concluded that, although the glutamine hypothesis may explain immunodepression related to other stressful conditions such as trauma and burn, plasma glutamine concentration is not likely to play a mechanistic role in exercise-induced immunodepression.

scholarly journals Mitosis in Cancer Cell Increases Immune Resistance via High Expression of HLA-G and PD-L1

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2661
Author(s):  
Matti Ullah ◽  
Warda Aoudjeghout ◽  
Cynthia Pimpie ◽  
Marc Pocard ◽  
Massoud Mirshahi
Keyword(s):  
Protein Expression ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
G1 Phase ◽  
G2 Phase ◽  
The Impact

Cancer is a result of “aggressive” division and uncontrolled proliferation of the abnormal cells that survive attack by immune cells. We investigated the expression of HLA-G and PD-L1 with the different stages of cancer cell division along with their role in the interaction of immune cells in vitro. Ovarian cancer (OVCAR-3) and chronic myeloid leukemia cell line (K-562) are used for this study. The correlation of protein expression with percentage of cells in each phase (G1, S and G2 phase) was evaluated through FACS. Cells were synchronized in G1, G2 and mitotic phase to evaluate gene (RT-qPCR) and protein expression (FACS). Real-time immune cell attack (RTICA) analysis with PBMCs (peripheral blood mono-nuclear cells) and cancer cells were performed. We found that cells expressing higher levels of HLA-G and PD-L1 are mainly in G2 phase and those expressing lower levels are mainly in G1 phase. Evidently, the higher expression of the two proteins was observed when synchronized in mitotic phase as compared to low expression when synchronized in G1 phase. RTICA analysis showed the presence of HLA-G delayed the lysis of the cells. In conclusion, the cancer cell can escape from immune cells in division stage that suggests the impact of mitosis index for cancer immunotherapy.

scholarly journals Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 198-201 ◽  
Author(s):  
JJ Hooks ◽  
BF Haynes ◽  
B Detrick-Hooks ◽  
LF Diehl ◽  
TL Gerrard ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Morphological Characteristics ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
T Cell Subsets ◽  
Ifn Gamma ◽  
Killer Activity ◽  
Human T Cell

Abstract We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T- cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.

scholarly journals HETEROGENEITY OF THE EFFECTOR CELLS IN THE CYTOTOXIC REACTION AGAINST ALLOGENEIC LYMPHOMA CELLS

1973 ◽  
Vol 137 (2) ◽  
pp. 369-386 ◽  
Author(s):  
James Forman ◽  
Sven Britton
Keyword(s):  
Immune Cells ◽  
Host Response ◽  
Marked Reduction ◽  
Cytotoxic Effect ◽  
Immune Serum ◽  
Spleen Cells ◽  
Effector Cells ◽  
Normal Spleen ◽  
Peak Phase

The cytotoxic effect of spleen cells from H-2 allogeneic mice was tested in vitro against an A strain leukemia (YAC) labeled with [125I]iododeoxyuridine. After the mice were primed with tumor cells, significant and specific H-2 immunity was detected on day 3 and peak cytotoxicity was observed between 7 and 14 days after priming. Two effector cells appear to be involved in the host response, because spleens taken from mice soon after priming were not sensitive to antitheta sera and complement while those taken during the peak stages of the response showed a marked reduction in cytotoxicity after treatment. Macrophages were not involved, since removal of these cells by the carbonyl iron method did not result in any reduction in cytotoxicity. Immune serum that was capable of inducing cell-mediated cytotoxicity in normal spleen cell populations also augmented cytotoxicity of spleen cells taken from mice primed 3 days previously. However, when spleen cells were taken from mice during the peak phase of the immune response, the same serum at the same dilutions inhibited the preexisting cytotoxicity. A difference was also detected in the killing efficiencies between early and late immune cells.

scholarly journals Immune cells as targets for cardioprotection: new players and novel therapeutic opportunities

2019 ◽  
Vol 115 (7) ◽  
pp. 1117-1130 ◽  
Author(s):  
Ioanna Andreadou ◽  
Hector A Cabrera-Fuentes ◽  
Yvan Devaux ◽  
Nikolaos G Frangogiannis ◽  
Stefan Frantz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Inflammatory Reaction ◽  
Immune Cells ◽  
Cell Response ◽  
Immune Cell ◽  
Left Ventricular ◽  
Lymphoid Cells ◽  
Inflammatory Phase ◽  
Anti Inflammatory ◽  
Immune Cell Response

Abstract New therapies are required to reduce myocardial infarct (MI) size and prevent the onset of heart failure in patients presenting with acute myocardial infarction (AMI), one of the leading causes of death and disability globally. In this regard, the immune cell response to AMI, which comprises an initial pro-inflammatory reaction followed by an anti-inflammatory phase, contributes to final MI size and post-AMI remodelling [changes in left ventricular (LV) size and function]. The transition between these two phases is critical in this regard, with a persistent and severe pro-inflammatory reaction leading to adverse LV remodelling and increased propensity for developing heart failure. In this review article, we provide an overview of the immune cells involved in orchestrating the complex and dynamic inflammatory response to AMI—these include neutrophils, monocytes/macrophages, and emerging players such as dendritic cells, lymphocytes, pericardial lymphoid cells, endothelial cells, and cardiac fibroblasts. We discuss potential reasons for past failures of anti-inflammatory cardioprotective therapies, and highlight new treatment targets for modulating the immune cell response to AMI, as a potential therapeutic strategy to improve clinical outcomes in AMI patients. This article is part of a Cardiovascular Research Spotlight Issue entitled ‘Cardioprotection Beyond the Cardiomyocyte’, and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

scholarly journals The Immune Endocannabinoid System of the Tumor Microenvironment

2020 ◽  
Vol 21 (23) ◽  
pp. 8929
Author(s):  
Melanie Kienzl ◽  
Julia Kargl ◽  
Rudolf Schicho
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Cells ◽  
Cannabinoid Receptors ◽  
Immune Cell ◽  
Tumor Development ◽  
Endocannabinoid System ◽  
Cell Functions ◽  
In Vitro Effects

Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system (ECS) may have an important role in shaping the TME. Members of the ECS, an entity that consists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive. This review/opinion discusses the possibility that the “immune endocannabinoid system” can fundamentally influence tumor progression. The widespread influence of cannabinoids on immune cell functions makes the members of the ECS an interesting target that could support immunotherapy.

scholarly journals Long Noncoding RNA in Myeloid and Lymphoid Cell Differentiation, Polarization and Function

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 269 ◽  
Author(s):  
Imran Ahmad ◽  
Araceli Valverde ◽  
Fayek Ahmad ◽  
Afsar Raza Naqvi
Keyword(s):  
Cell Differentiation ◽  
Immune Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Immune Cell ◽  
Lymphoid Cells ◽  
Tissue Cell ◽  
Specific Expression ◽  
And Function

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

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