scholarly journals Immunomodulatory Effects of Cyperus rotundus Extract on 7,12 Dimethylbenz[a]anthracene (DMBA) Exposed BALB/c Mice

2020 ◽  
Vol 27 (1) ◽  
pp. 46-55
Author(s):  
Abu Hanifah Ramadhani ◽  
Wirdatun Nafisah ◽  
Hary Isnanto ◽  
Tri Kurniawati Sholeha ◽  
Yoga Dwi Jatmiko ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Inflammatory Cytokines ◽  
Cd8 T Cells ◽  
Graphical Analysis ◽  
Tumor Formation ◽  
Cyperus Rotundus ◽  
Carcinogenic Substance ◽  
Activated T Lymphocytes ◽  
Pro Inflammatory Cytokines

Background: The carcinogenic substance 7,12-Dimethylbenz[a]anthracene (DMBA) was commonly used to induce tumor formation in rodents. The development of tumor may trigger higher expression of pro-inflammatory cytokines, which in turn supports tumor progression. In this study, we examined the efficacy of Cyperus rotundus extract (CRE) that was reported to have anti-inflammatory properties. We focused on investigating the levels of activated T lymphocytes and the pro-inflammatory cytokines expressed by macrophages. Methods: Female BALB/c were injected with DMBA subcutaneously. The DMBA exposed mice were given CRE orally in three different doses; 63.33, 158.4, and 316.8 mg/kg. After 14 days, the levels of activated T lymphocytes and pro-inflammatory cytokines were analyzed using flow cytometry. Graphical analysis was done with FlowJo v10 and followed by statistical analysis. Results: The treatment of CRE reduced the population of CD4 and CD8 T cells. The number of activated CD4 and CD8 T cells were also significantly suppressed. The population of macrophages marked by CD11b cells was significantly reduced. Finally, the CRE treatment suppressed the levels of TNF-α, IFN-γ, IL-1β, and IL-6 expressed by macrophages. Conclusion: Our findings suggest that CRE could be a potential agent useful in therapeutic approaches for curing the disease caused by aberrant cells.

A Phase I/II Study of IPH1101 (BrHPP), Specific Agonist of Vã9Vä2 T Lymphocytes, in Combination with Rituximab Re-Treatment in Patients with Follicular Lymphoma. Interim Phase I Data.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1002-1002
Author(s):  
Guy Laurent ◽  
Jean François Rossi ◽  
Eric W Van Den Neste ◽  
Fabien Audibert ◽  
Hervé Ghesquières ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Phase I ◽  
Follicular Lymphoma ◽  
Dose Level ◽  
Inflammatory Cytokines ◽  
Γδ T Cells ◽  
Low Doses ◽  
Grade 3 ◽  
Pro Inflammatory Cytokines

Abstract Background: Unconventional γδ T lymphocytes are innate immunity effectors bearing very strong anti-tumoral activity. Previous studies have documented that malignant B cells are highly sensitive to γδ T cells mediated cellular toxicity. IPH1101 is a chemically-synthesized, specific antigen for γδ T cells: IPH1101 triggers the synthesis of pro-inflammatory cytokines by γδ T cells - inducing the recruitment of other cell effectors and facilitating implementation of an adaptive response - and potentiates the direct cytotoxic activity of γδ T cells against a large number of tumor B-cell lines. Also, IPH1101-activation of γδ T cells in the presence of low doses of IL-2 leads to their proliferation and differentiation into effectors capable of mediating ADCC. ADCC is the main known molecular mechanism underlying rituximab bioactivity. Increasing the number and the activation of killer lymphocytes mediating ADCC is crucial for therapeutic potency and deserves to be tested in a clinical trial. The purpose of this study is to assess the clinical efficacy, the biological activity, and the safety of the association of IPH1101 with low doses of IL-2, combined to a standard rituximab re-treatment, in patients with Follicular Lymphoma. Method: This is an open label, multinational study consisting of a Phase I like dose-escalation part, followed by Phase II part. Here are reported the Phase I part results. The study population is patients presenting Follicular non-Hodgkin’s Lymphoma, relapsing after 1 or 2 lines of previous therapy, with at least 1 rituximab-containing line. Rituximab (375 mg/m2) was administered 4 times weekly. IPH1101 (750 mg/m2) was administered i.v. three times (every 3 weeks), the first administration being one day after the second rituximab infusion. IL-2 courses consisted in s.c. daily administrations for 5 days, starting on the same day of each IPH1101 administration. All patients participating in this Phase I like period were to be enrolled sequentially with an interval of at least 15 days for evaluation of potential dose limiting toxicity (DLT) occurrence. Results: Six patients were part of the phase I: 3 at IL-2 dose level of 4 MIU and 3 at IL-2 dose level 8 MIU, the targeted dose. No patient presented a DLT as defined in the protocol. One patient treated at the dose level of 8 MIU withdrew the study treatment after the second administration of IL-2 of cycle 2 mainly due to grade 3 asthenia (SAE) and grade 2 vomiting and epigastralgia. At dose level IL-2 of 4 MIU, 2 SAEs were reported: a grade 3 hypotension and a grade 3 ALAT elevation. Most reported adverse events were mild or moderate, mainly nausea, IL-2 injection site reaction, vomiting, diarrhoea, and grade 1 or 2 pyrexia. Their frequency was higher in the cohort treated with 8 MIU of IL2. Pharmacology of IPH1101/IL-2 in this phase I part, based on a weekly monitoring of blood γδ T cells and on dosages of early released plasma cytokines, shows γδ T cells are very efficiently expanded, in an IL-2 dose-dependent fashion and with slow return to baseline. Pro-inflammatory cytokines are released at each IPH1101/IL-2 injections. No unexpected immuno-biological event was reported. Conclusion: These observations showing a good safety and immuno-biological efficacy profile of the combination of rituximab, IPH1101 and low dose IL-2, have allowed the start of the Phase II part of the study with IPH1101/ IL-2 dose of 8 MIU combined with rituximab in patients with follicular lymphoma. The recruitment is ongoing.

scholarly journals Myxoma virus suppresses proliferation of activated T lymphocytes yet permits oncolytic virus transfer to cancer cells

Blood ◽  
2015 ◽  
Vol 125 (24) ◽  
pp. 3778-3788 ◽  
Author(s):  
Nancy Y. Villa ◽  
Clive H. Wasserfall ◽  
Amy M. Meacham ◽  
Elizabeth Wise ◽  
Winnie Chan ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cancer Cells ◽  
Inflammatory Cytokines ◽  
Oncolytic Virus ◽  
Myxoma Virus ◽  
Human T Lymphocytes ◽  
Virus Transfer ◽  
Key Points ◽  
Activated T Lymphocytes

Key Points MYXV binds human T lymphocytes but does not enter and infect T cells until after activation. MYXV-infected T lymphocytes proliferate less and secrete less inflammatory cytokines but deliver oncolytic virus to augment GVM.

scholarly journals A rat model of mild intestinal inflammation induced byStaphylococcus aureusenterotoxin B

2010 ◽  
Vol 69 (3) ◽  
pp. 447-453 ◽  
Author(s):  
Anna Pérez-Bosque ◽  
Miquel Moretó
Keyword(s):  
T Lymphocytes ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Plasma Proteins ◽  
Intestinal Inflammation ◽  
Killer Cell ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Activated T Lymphocytes ◽  
Pro Inflammatory Cytokines

The epithelial barrier of the intestine and the gut-associated lymphoid tissue (GALT) protects the host against luminal pathogenic micro-organisms. This is important at weaning, when animals are exposed to infectious agents and stresses. We have developed a rat model of intestinal inflammation post weaning, based on the systemic administration ofStaphylococcus aureusenterotoxin B (SEB). Since the inflammatory response obtained is mild, the food intake pattern is not affected, which makes this model useful for studies of nutritional therapies for intestinal inflammatory disease. SEB increased T-lymphocytes in Peyer's patches and the number of activated T-lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria, SEB increased activated T-lymphocytes as well as cytotoxic and natural killer-cell populations of the diffuse GALT. It also increased pro-inflammatory cytokines and inflammatory mediators in both Peyer's patches and mucosa. Rats given SEB had higher paracellular permeability to macromolecules, which was associated with a reduction in epithelial tightness. This model was used to examine whether dietary supplementation with spray-dried animal plasma proteins affects intestinal inflammation. Results showed that dietary plasma proteins can attenuate the mucosal immune response in both organized and diffuse GALT and that these effects are mediated by a reduction in the production of pro-inflammatory cytokines.

Liposome-encapsulated HIV-1 Gag p24 containing lipid A induces effector CD4+ T-cells, memory CD8+ T-cells, and pro-inflammatory cytokines

Vaccine ◽  
2009 ◽  
Vol 27 (49) ◽  
pp. 6939-6949 ◽  
Author(s):  
Nicholas J. Steers ◽  
Kristina K. Peachman ◽  
Sasha McClain ◽  
Carl R. Alving ◽  
Mangala Rao
Keyword(s):  
T Cells ◽  
Inflammatory Cytokines ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lipid A ◽  
Memory Cd8 T Cells ◽  
Hiv 1 ◽  
Pro Inflammatory Cytokines

scholarly journals CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

2004 ◽  
Vol 200 (11) ◽  
pp. 1407-1417 ◽  
Author(s):  
Adrian F. Ochsenbein ◽  
Stanley R. Riddell ◽  
Michele Brown ◽  
Lawrence Corey ◽  
Gabriela M. Baerlocher ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Effector Memory ◽  
Term Survival ◽  
Functional Consequences

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response.

Specific features of T- and NK-cellular immunity in chronic lymphocytic leukemia

2021 ◽  
Vol 66 (6) ◽  
pp. 345-352
Author(s):  
Evgeniy Vladimirovich Pochtar ◽  
S. A. Lugovskaya ◽  
E. V. Naumova ◽  
E. A. Dmitrieva ◽  
A. I. Kostin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Lymphocytic Leukemia ◽  
Positive Trend ◽  
Functional Changes ◽  
Activated T Lymphocytes ◽  
T Helpers

Profound immunological dysfunction is the key factor determining the development of infectious complications in chronic lymphocytic leukemia (CLL). The aim of this work is to assess the features of the subpopulation composition of T-lymphocytes (T-helpers (Th), cytotoxic T-lymphocytes (Tcyt), T regulatory cells (Treg), T-NK cells, naive Th, Th-memory, activated T-lymphocytes, TCRγδ cells) and NK cells in peripheral blood of patients with newly diagnosed chronic lymphocytic leukemia (CLL) and receiving ibrutinib therapy. Hematological and immunophenotypic studies have been performed in 30 patients with previously untreated CLL, 122 patients on ibrutinib therapy and 20 healthy donors. The subpopulation composition of T-lymphocytes (Th, Tcyt, Treg, T-NK, naive T-helpers, memory T-helpers, TCRγδ cells, activated T-lymphocytes) and NK cells has been assessed on flow cytometer (FACSCanto II (BD)) using the following panel of monoclonal antibodies: CD45, CD19, CD3, CD4, CD5, CD8, TCRγδ, CD127, CD16, CD56, CD57 CD45RA, CD45R0, HLA-DR, CD25. Compared to controls all CLL samples were found to have higher the absolute number of T-lymphocytes, NK cells and their subpopulations, T-helpers (especially of memory T-cells), cytotoxic T-cells, regulatory T-cells, TCRγδ T-cells, activated T-lymphocytes, increased cytotoxic potential of NK cells in previously untreated CLL patients. Patients who received ibrutinib therapy have registered a positive trend towards recovery of the subpopulation composition of T-lymphocytes and NK-cells. CLL patients have been found to have quantitative and functional changes in the subpopulations of T-lymphocytes and NK cells, indicating dysregulation of the immune response, and a high risk of developing infections. Monitoring of immunological parameters for ibrutinib therapy make possible to estimate impact of ibrutinib on the adaptive anti-CLL immune response.

scholarly journals Depletion of CD8αβ+ T Cells in Chickens Demonstrates Their Involvement in Protective Immunity towards Marek’s Disease with Respect to Tumor Incidence and Vaccinal Protection

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 557
Author(s):  
Supawadee Umthong ◽  
John R. Dunn ◽  
Hans H. Cheng
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Lymphoproliferative Disease ◽  
Tumor Formation ◽  
Marek's Disease ◽  
Control Measures ◽  
Marek’S Disease ◽  
Cell Mediated Immune Response

Marek’s disease (MD) is a lymphoproliferative disease in chickens caused by Marek’s disease virus (MDV), a highly oncogenic alphaherpesvirus. Since 1970, MD has been controlled through widespread vaccination of commercial flocks. However, repeated and unpredictable MD outbreaks continue to occur in vaccinated flocks, indicating the need for a better understanding of MDV pathogenesis to guide improved or alternative control measures. As MDV is an intracellular pathogen that infects and transforms CD4+ T cells, the host cell-mediated immune response is considered to be vital for controlling MDV replication and tumor formation. In this study, we addressed the role of CD8+ T cells in vaccinal protection by widely-used monovalent (SB-1 and HVT) and bivalent (SB-1+HVT) MD vaccines. We established a method to deplete CD8+ T cells in chickens and found that their depletion through injection of anti-CD8 monoclonal antibodies (mAb) increased tumor induction and MD pathology, and reduced vaccinal protection to MD, which supports the important role of CD8+ T cells for both MD and vaccinal protection.

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

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