scholarly journals Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2619-2625 ◽  
Author(s):  
JW Semple ◽  
J Freedman
Keyword(s):  
Peripheral Blood ◽  
T Helper Cells ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Autoimmune Disorder ◽  
T Helper ◽  
Phenotypic Analysis ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Helper Cells

Chronic autoimmune thrombocytopenic purpura (ATP) is a common hematologic disorder in which platelet-specific autoantibodies bind to platelets and enhance their destruction by the reticuloendothelial system. While there has been considerable investigation of the humoral immune abnormalities in ATP, little work has been performed on the cellular immunoregulatory aspects of this autoimmune disorder. We describe here that patients with ATP have lymphocytes that proliferate normally when stimulated by mitogens. However, when stimulated by normal control platelets in 7-day antigen-presenting cell cultures, peripheral blood mononuclear cells (PBMC) from patients with ATP proliferate at significantly higher levels (P less than .001) and their lymphocytes secrete significantly higher amounts of interleukin-2 (IL- 2) (P less than .001) than do lymphocytes from control subjects. Depletion studies with monoclonal anti-CD8 and complement did not reduce the proliferative capacity of the responding PBMC population, indicating that CD4+ T-helper cells may be responsible for the response. Phenotypic analysis of peripheral blood lymphocyte subsets from patients with ATP showed that there was a significant reduction in CD4+Leu8+ T suppressor-inducer cells (P less than .001) and a concomitant increase in CD3+DR+ activated T cells (P less than .001) and CD19+ B cells (P less than .05). These data indicate that CD4+ T- helper cells from patients with ATP are stimulated by normal platelet antigen(s) to secrete IL-2 and may modulate the enhanced antiplatelet autoantibody response.

scholarly journals Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2619-2625 ◽  
Author(s):  
JW Semple ◽  
J Freedman
Keyword(s):  
Peripheral Blood ◽  
T Helper Cells ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Autoimmune Disorder ◽  
T Helper ◽  
Phenotypic Analysis ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Helper Cells

Abstract Chronic autoimmune thrombocytopenic purpura (ATP) is a common hematologic disorder in which platelet-specific autoantibodies bind to platelets and enhance their destruction by the reticuloendothelial system. While there has been considerable investigation of the humoral immune abnormalities in ATP, little work has been performed on the cellular immunoregulatory aspects of this autoimmune disorder. We describe here that patients with ATP have lymphocytes that proliferate normally when stimulated by mitogens. However, when stimulated by normal control platelets in 7-day antigen-presenting cell cultures, peripheral blood mononuclear cells (PBMC) from patients with ATP proliferate at significantly higher levels (P less than .001) and their lymphocytes secrete significantly higher amounts of interleukin-2 (IL- 2) (P less than .001) than do lymphocytes from control subjects. Depletion studies with monoclonal anti-CD8 and complement did not reduce the proliferative capacity of the responding PBMC population, indicating that CD4+ T-helper cells may be responsible for the response. Phenotypic analysis of peripheral blood lymphocyte subsets from patients with ATP showed that there was a significant reduction in CD4+Leu8+ T suppressor-inducer cells (P less than .001) and a concomitant increase in CD3+DR+ activated T cells (P less than .001) and CD19+ B cells (P less than .05). These data indicate that CD4+ T- helper cells from patients with ATP are stimulated by normal platelet antigen(s) to secrete IL-2 and may modulate the enhanced antiplatelet autoantibody response.

Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment

2016 ◽  
Vol 23 (4) ◽  
pp. 567-576 ◽  
Author(s):  
Ulrike Bühler ◽  
Vinzenz Fleischer ◽  
Felix Luessi ◽  
Ayman Rezk ◽  
Patrick Belikan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Healthy Controls ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Helper Cells

Objective: Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity. Methods: Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients ( n = 33), untreated RRMS patients ( n = 13), and healthy controls ( n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients. Results: Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-γ+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed. Conclusion: Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug’s mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.

scholarly journals Limited Applicability of GW9662 to Elucidate PPARγ-Mediated Fatty Acid Effects in Primary Human T-Helper Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Anke Jaudszus ◽  
Stefan Lorkowski ◽  
Michael Gruen ◽  
Alexander Roth ◽  
Gerhard Jahreis
Keyword(s):  
Fatty Acid ◽  
T Helper Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Inhibitory Effect ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Helper Cells ◽  
Mechanistic Investigation ◽  
Limited Applicability

Synthetic antagonists of the nuclear receptor PPARγsuch as GW9662 are widely used to elucidate receptor-mediated ligand effects. In addition and complementary to recent work, we examined whether GW9662 is suitable to serve for mechanistic investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC) were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10 μmol/L) 30 min before adding thec9,t11-isomer of conjugated linoleic acid (c9,t11-CLA) as representative of PPARγ-activating fatty acids with immunomodulatory properties. Corresponding cultures were incubated with GW9662 in the absence of the fatty acid. After 19 h, cells were mitogen stimulated for further 5 h. Subsequently, intracellular IL-2 was measured in CD3+CD4+lymphocytes by means of flow cytometry. 100 μmol/Lc9,t11-CLA reduced the number of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty acid effect, likely due to the fact that the compound exerted an own inhibitory effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death in human leukocytes. These results suggest that application of GW9662 is not conducive in this experimental setting.

scholarly journals Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1

2021 ◽  
Vol 22 (15) ◽  
pp. 7988
Author(s):  
Andrea Coppola ◽  
Barbara Capuani ◽  
Francesca Pacifici ◽  
Donatella Pastore ◽  
Roberto Arriga ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Interleukin 2 ◽  
High Mobility ◽  
High Mobility Group ◽  
Low Grade ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Activation of innate immunity and low-grade inflammation contributes to hyperglycemia and an onset of Type 2 Diabetes Mellitus (T2DM). Interleukin-2 (IL-2), leptin, High Mobility Group Box-1 (HMGB-1), and increased glucose concentrations are mediators of these processes also by modulating peripheral blood mononuclear cells (PBMCs) response. The aim of this study was to investigate if HMGB-1 and IL-2 turn on PBMCs and their leptin secretion. In isolated human PBMCs and their subpopulations from healthy individuals and naïve T2DM patients, leptin release, pro-inflammatory response and Toll-like Receptors (TLRs) activation was measured. After treatment with IL-2 and HMGB1, NK (Natural Killer) have the highest amount of leptin secretion, whilst NK-T have the maximal release in basal conditions. TLR4 (TAK242) and/or TLR2 (TLR2-IgA) inhibitors decreased leptin secretion after IL-2 and HMGB1 treatment. A further non-significant increase in leptin secretion was reported in PBMCs of naive T2DM patients in response to IL-2 and HMGB-1 stimulation. Finally, hyperglycemia or hyperinsulinemia might stimulate leptin secretion from PBMCs. The amount of leptin released from PBMCs after the different treatments was enough to stimulate the secretion of IL-1β from monocytes. Targeting leptin sera levels and secretion from PBMCs could represent a new therapeutic strategy to counteract metabolic diseases such as T2DM.

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 The state of immune system during the use of probiotic lactobacilli in complex treatment of papillomavirus infection

2017 ◽  
Vol 98 (1) ◽  
pp. 20-26 ◽  
Author(s):  
A G Borisov ◽  
A A Savchenko ◽  
E P Tihonova ◽  
I V Sergeeva ◽  
E V Kasparov ◽  
...  
Keyword(s):  
Nk Cells ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Standard Therapy ◽  
Reproductive Age ◽  
Reference Level ◽  
T Helper ◽  
Helper Cells ◽  
Papillomavirus Infection ◽  
Probiotic Lactobacilli

Aim. Assessment of impact of probiotic lactobacilli complex on treatment efficiency and normalization of immune status in women with human papillomavirus infection (PVI).Methods. Total of 65 patients of reproductive age with cervical pathology and PVI were examined. «Provag» was included into the standard therapy as the source of probiotic lactobacilli complex. Immunological studies were conducted before and after the treatment. The phenotypic profile of peripheral blood lymphocytes was determined by means of flow cytometry. The concentration of immunoglobulin A, G and M in serum was determined by ELISA.Results. Decreased amounts of T- and NK-cells were observed in PVI patients on day 1. Regardless of treatment method, by day 30 the number of T-lymphocytes in the blood of women with PVI increases. Percentage of NK-cells remained below the normal values on day 30 in the group of patients who received traditional scheme of PVI treatment. Patients with PVI taking additionally probiotic lactobacilli complex showed an increase of NK-cells by the end of the treatment. On day 1 decrease of relative and absolute numbers of T-helper cells was detected. Regardless of the method of treatment by day 30 the number of T-helper cells increases to the reference level. IgM and IgG levels in peripheral blood of women with PVI were increased even on day 1. By the end of the observation period their concentration in patients with conventional treatment scheme remained increased. Patients receiving the standard therapy supplemented with «Provag» demonstrated the decrease of these classes of immunoglobulins to the reference level.Conclusion. As a result of treatment normalization of NK-cells and T-helpers numbers was observed whereas the IgG and IgM levels remained increased.

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