scholarly journals Induction of Fas (Apo-1, CD95)-Mediated Apoptosis of Activated Lymphocytes by Polyclonal Antithymocyte Globulins

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2360-2368 ◽  
Author(s):  
Laurent Genestier ◽  
Sylvie Fournel ◽  
Monique Flacher ◽  
Olga Assossou ◽  
Jean-Pierre Revillard ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Resting Cells ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Gene And Protein Expression ◽  
Fas L ◽  
Induced Apoptosis

Polyclonal horse antilymphocyte and rabbit antithymocyte globulins (ATGs) are currently used in severe aplastic anemia and for the treatment of organ allograft acute rejection and graft-versus-host disease. ATG treatment induces a major depletion of peripheral blood lymphocytes, which contributes to its overall immunosuppressive effects. Several mechanisms that may account for lymphocyte lysis were investigated in vitro. At high concentrations (.1 to 1 mg/mL) ATGs activate the human classic complement pathway and induce lysis of both resting and phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells. At low, submitogenic, concentration ATGs induce antibody-dependent cell cytotoxicity of PHA-activated cells, but not resting cells. They also trigger surface Fas (Apo-1, CD95) expression in naive T cells and Fas-ligand gene and protein expression in both naive and primed T cells, resulting in Fas/Fas-L interaction-mediated cell death. ATG-induced apoptosis and Fas-L expression were not observed with an ATG preparation lacking CD2 and CD3 antibodies. Susceptibility to ATG-induced apoptosis was restricted to activated cells, dependent on IL-2, and prevented by Cyclosporin A, FK506, and rapamycin. The data suggest that low doses of ATGs could be clinically evaluated in treatments aiming at the selective deletion of in vivo activated T cells in order to avoid massive lymphocyte depletion and subsequent immunodeficiency.

scholarly journals Induction of Fas (Apo-1, CD95)-Mediated Apoptosis of Activated Lymphocytes by Polyclonal Antithymocyte Globulins

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2360-2368 ◽  
Author(s):  
Laurent Genestier ◽  
Sylvie Fournel ◽  
Monique Flacher ◽  
Olga Assossou ◽  
Jean-Pierre Revillard ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Resting Cells ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Gene And Protein Expression ◽  
Fas L ◽  
Induced Apoptosis

Abstract Polyclonal horse antilymphocyte and rabbit antithymocyte globulins (ATGs) are currently used in severe aplastic anemia and for the treatment of organ allograft acute rejection and graft-versus-host disease. ATG treatment induces a major depletion of peripheral blood lymphocytes, which contributes to its overall immunosuppressive effects. Several mechanisms that may account for lymphocyte lysis were investigated in vitro. At high concentrations (.1 to 1 mg/mL) ATGs activate the human classic complement pathway and induce lysis of both resting and phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells. At low, submitogenic, concentration ATGs induce antibody-dependent cell cytotoxicity of PHA-activated cells, but not resting cells. They also trigger surface Fas (Apo-1, CD95) expression in naive T cells and Fas-ligand gene and protein expression in both naive and primed T cells, resulting in Fas/Fas-L interaction-mediated cell death. ATG-induced apoptosis and Fas-L expression were not observed with an ATG preparation lacking CD2 and CD3 antibodies. Susceptibility to ATG-induced apoptosis was restricted to activated cells, dependent on IL-2, and prevented by Cyclosporin A, FK506, and rapamycin. The data suggest that low doses of ATGs could be clinically evaluated in treatments aiming at the selective deletion of in vivo activated T cells in order to avoid massive lymphocyte depletion and subsequent immunodeficiency.

scholarly journals B Cells of HIV-1–Infected Patients Bind Virions through Cd21–Complement Interactions and Transmit Infectious Virus to Activated T Cells

2000 ◽  
Vol 192 (5) ◽  
pp. 637-646 ◽  
Author(s):  
Susan Moir ◽  
Angela Malaspina ◽  
Yuexia Li ◽  
Tae-Wook Chun ◽  
Tomeka Lowe ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphoid Tissues ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
The Impact ◽  
Hiv 1 ◽  
Hiv Negative

The impact of HIV-associated immunopathogenesis on B cells has been largely associated with indirect consequences of viral replication. This study demonstrates that HIV interacts directly with B cells in both lymphoid tissues and peripheral blood. B cells isolated from lymph node and peripheral blood mononuclear cells (PBMCs) of 4 and 23 chronically infected patients, respectively, demonstrated similar capacities to pass virus to activated HIV-negative PBMCs when compared with CD4+ cells from the same patients. However, in contrast to T cells, virus associated with B cells was surface bound, as shown by its sensitivity to pronase and the staining pattern revealed by in situ amplification of HIV-1 RNA. Cell sorting and ligand displacing approaches established that CD21 was the HIV-binding receptor on B cells, and that this association was mediated through complement-opsonized virus. These B cells were also found to express significantly lower levels of CD21 compared with HIV-negative individuals, suggesting a direct perturbing effect of HIV on B cells. These findings suggest that B cells, although they themselves are not readily infected by HIV, are similar to follicular dendritic cells in their capacity to serve as extracellular reservoirs for HIV-1. Furthermore, B cells possess the added capability of circulating in peripheral blood and migrating through tissues where they can potentially interact with and pass virus to T cells.

Systemic modulatory effects of the treatment with IL-2 of lung metastasis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2560-2560
Author(s):  
D. Diaz ◽  
L. Chara ◽  
J. Chevarria ◽  
V. Navas ◽  
E. Esteban ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Renal Carcinoma ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Wilcoxon Test ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Before And After ◽  
Induced Apoptosis

2560 Background: IL-2 is a drug that is employed in the treatment of several tumors due to its capacity of restore or increase the regulatory and effector function of the immune system. These effects have been demonstrated with the administration of the drug by intravenous and subcutaneous ways. Recently, it has been observed that the inhaled IL-2 administration is effective in the treatment of lung and renal cell carcinoma metastasis. However, it is unknown if this therapeutic effect is accompanied of systemic and local modulatory effects. Objectives: To compare spontaneous and mitogen-induced apoptosis in lymphocytes of renal carcinoma patients before and after treatment with inhaled IL-2. Methods: Peripheral blood mononuclear cells were purified from 7 patients with renal carcinoma before and after treatment with inhaled IL-2. The cells were characterized in a FACScalibur analyzer using fluorocrome-labeled monoclonal antibodies. The AI (or percentage of apoptotic cells, AI x 100) was calculated for T-cells expressing CD3, CD4, CD8, CD56, HLA-DR, CD25 and CD45RO/CD45RA antigens and NK-cells (CD3-CD56+ or CD3-CD16+). These AI were determined after 24 hours of culture under two conditions: without exogenous apoptosis inducers and in the presence of phytohemagglutinin. Comparisons between patients were carried out using the Wilcoxon test and were considered significant when p < 0.05. Results: A significant decrease in spontaneous ex vivo apoptosis was found in peripheral blood lymphocytes from renal carcinoma patients after treatment with inhaled IL-2 with respect to pretreatment values. This decrease occurred in T-cells and also in CD45RO expressing cells from both CD4+ and CD8+ subsets. A decrease of apoptosis was also observed in CD25+ expressing cells from CD3+, CD4+ and CD8+ subsets. A decrease in AI was found in mitogen induced apoptosis of CD25+ cells from CD3+, CD4+ and CD8+ subsets. Conclusions: The treatment with inhaled IL-2 has immunomodulatory effects that are observed at systemic level reducing the apoptosis of cells from several memory and activated T-cell subsets. No significant financial relationships to disclose.

Preventive Cancer Vaccination by P5 HER-2/neo Derived Peptide‐pulsed Peripheral Blood Mononuclear Cells in Mouse Model of Breast Cancer

2021 ◽  
Author(s):  
Mahdi Dehghan-Manshadi ◽  
Amin Reza Nikpoor ◽  
Hossein Hadinedoushan ◽  
Fateme Zare ◽  
Mojtaba Sankian ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Mrna Levels ◽  
Mice Model ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

This study aimed to compare the prophylactic effects of dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) based vaccines by pulsing them in vitro with p5 peptide. The different groups of mice were injected by free peptide or peptide pulsed with DCs or PBMCs. Two weeks after the last boosting dose, immunological tests were performed on splenocyte suspensions of three mice, and the remaining mice in each group were evaluated for tumor growth and survival. The IFN-γ, granzyme B, and IL-10 were detected in T cells. Additionally, IFN-γ and perforin as well as mRNA levels of some genes associated with immune responses were assessed after challenging of splenocytes with TUBO cells. A significant increase was observed in frequency of CD4+ IFN-γ+, CD8+ IFN-γ+ and CD8+ granzymeB+ T cells, and the perforin of supernatants in DC and PBMC groups. A significant Fas ligand (FasL) and forkhead box P3 (Foxp3) expression was observed in DC and PBMC groups. These responses led to lower tumor sizes and longer survival time in tumor mice model. The efficacy of this PBMC-based vaccine in improving the protective immune response makes it a simpler and less expensive candidate vaccine compared to DCs-based vaccines.

scholarly journals Increased CCR7loPD-1hiCXCR5+CD4+ T Cells in Peripheral Blood Mononuclear Cells Are Correlated with Immune Activation in Patients with Chronic HBV Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Ya-Xin Huang ◽  
Qi-Yi Zhao ◽  
Li-Li Wu ◽  
Dong-Ying Xie ◽  
Zhi-Liang Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
Peripheral Blood Mononuclear ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
Chronic Hbv ◽  
Immune Tolerant

T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.

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