scholarly journals Altered expressions of CXCR4 and CD26 on T-helper lymphocytes in hereditary hemorrhagic telangiectasia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alexandre Guilhem ◽  
Pierre Portalès ◽  
Sophie Dupuis-Girod ◽  
Sophie Rivière ◽  
Thierry Vincent
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Case Series ◽  
Severe Infection ◽  
Intravenous Iron ◽  
Surface Expression ◽  
Cytotoxic Lymphocytes ◽  
T Helper ◽  
Membrane Expression ◽  
Susceptibility To Infection ◽  
T Helper Lymphocytes

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (muco-cutaneous telangiectases, arteriovenous malformations), a specific risk of infection is suggested by case series of severe and atypical infections as well as by reports of decreased T and natural killer (NK) lymphocyte counts. As some evidence supports a dysregulation of the CXCR4/CXCL12 chemotactic axis of HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes. Methods Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating T-helper and T-cytotoxic lymphocytes (including naive, memory and activated subsets) and NK cells. Results The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs. 1026 cells/mm3, p < 0.0001), correlated with age (r =  − 0.46, p = 0.005), requirement of intravenous iron or blood transfusions (median: 291 vs. 627 cells/mm3, p = 0.03) and CXCR4 surface expression (r = 0.353, p = 0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs. 5.74 for CXCR4 and 3.21 vs. 4.33 for CD26, p = 0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the total T-lymphocyte population, as well as on the T-helper population and its naive subset (median on naive T-helper cells: 2.34 vs. 1.32, p = 0.0002). Conclusions Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.

Altered Expressions of CXCR4 and CD26 On T-Helper Lymphocytes in Hereditary Hemorrhagic Telangiectasia

2021 ◽  
Author(s):  
Alexandre GUILHEM ◽  
Pierre Portalès ◽  
Sophie Dupuis-Girod ◽  
Sophie Rivière ◽  
Thierry Vincent
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Severe Infection ◽  
Intravenous Iron ◽  
Surface Expression ◽  
T Helper ◽  
Membrane Expression ◽  
Susceptibility To Infection ◽  
T Helper Lymphocytes ◽  
Infectious Risk ◽  
Healthy Control

Abstract Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (telangiectasia, arteriovenous malformations), patients exhibit a specific infectious risk and a deficit of T and natural killer (NK) lymphocytes. As the CXCR4/CXCL12 chemotactic axis is dysregulated in HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes.Results: Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating helper and cytotoxic T lymphocytes (including naive, memory and activated subsets) and NK cells.The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs 1026 cells/mm3, p<0.0001), correlated with age (r=-0.46, p=0.005), requirement of intravenous iron or blood transfusions (median: 291 vs 627 cells/mm3, p=0.03) and CXCR4 surface expression (r=0.353, p=0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs 5.74 for CXCR4 and 3.21 vs 4.33 for CD26, p=0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the naive T-helper lymphocytes (median: 2.34 vs 1.32, p=0.0002), also observed on the T and T-helper populations.Conclusions: Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.

scholarly journals T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Giuseppe Losurdo ◽  
Domenico Piscitelli ◽  
Federica Pezzuto ◽  
Francesco Fortarezza ◽  
Claudia Covelli ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Intraepithelial Lymphocytes ◽  
Duodenal Biopsy ◽  
Cytotoxic Lymphocytes ◽  
Gluten Sensitivity ◽  
T Helper ◽  
T Helper Lymphocytes ◽  
T Helper Lymphocyte ◽  
Few Data ◽  
Negative Controls

Background and Aims. Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation. Materials and Methods. We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni’s tests were used for statistical analysis. Results. Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes; p<0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm2; p<0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes, p<0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm2; p=0.009). Conclusions. The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS.

Cellular immune response of pigeons in the conditions of endotoxin fever and pyrogenic tolerance

2011 ◽  
Vol 14 (1) ◽  
pp. 127-133 ◽  
Author(s):  
K. Dudek ◽  
D. Bednarek
Keyword(s):  
Immune Response ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Physiological Saline ◽  
Peripheral Blood Lymphocytes ◽  
Cytotoxic Lymphocytes ◽  
T Helper ◽  
T Helper Lymphocytes ◽  
Immunological Assays ◽  
Cellular Immune

Cellular immune response of pigeons in the conditions of endotoxin fever and pyrogenic toleranceThe aim of this study was to investigate changes in selected parameters of cellular immune response in the conditions of endotoxin fever and pyrogenic tolerance in pigeons. On the first day of observation the experimental birds (n=18) were intravenously injected withEscherichia coliLPS at a dose of 10 μg/kg b.w., while the control animals (n=6) received apyrogenic physiological saline also in the form of injection. On the second and the third day of the experiment LPS was injected additionally at 24 h intervals. Four and a half hours after the saline and pyrogen administration blood samples were collected from the control and experimental pigeons. The following immunological assays were performed: WBC, leucogram and immunophenotyping of lymphocyte subsets in peripheral blood, i.e. CD 3+(T lymphocytes), CD 4+(T helper lymphocytes) and CD 8+(T suppressor/ cytotoxic lymphocytes) cells. In the conditions of endotoxin fever (i.e. after the first LPS injection) leucopenia, monocytopenia, heterophilia and eosinophilia were observed. Additionally, the immunophenotyping of peripheral blood lymphocytes indicated an increase in percentage of CD 3+, CD 4+and CD 8+cells in response to the single injection of LPS. In contrast, the consecutive injections of LPS, which created a pyrogenic tolerance effect, caused a decrease in WBC value, heteropenia, eosinopenia and lymphocytosis. Moreover, during this state an increase in percentage of CD 3+and CD 8+cells was demonstrated in contrast to the percentage of CD 4+lymphocytes. The general tendencies in cellular immune response of the affected pigeons in the conditions of endotoxin fever and pyrogenic tolerance aim at activation of defence mechanisms against LPS for its prompt elimination from the animal's organism.

Interleukin 18 (IL-18) as a target for immune intervention.

2016 ◽  
Vol 63 (1) ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska ◽  
Magdalena Kowalewicz-Kulbat ◽  
Wieslawa Rudnicka
Keyword(s):  
Surface Expression ◽  
Dependent Manner ◽  
Interleukin 18 ◽  
T Helper ◽  
Immune Intervention ◽  
Inhibitory Protein ◽  
Ifn Gamma ◽  
Potent Inducer ◽  
Cell Responses ◽  
Th 1

Interleukin 18 (IL-18) is a pleiotropic cytokine involved in the regulation of innate and acquired immune response. In the milieu of IL-12 or IL-15, IL-18 is a potent inducer of IFN-gamma in natural killer (NK) cells and CD4 T helper (Th) 1 lymphocytes. However, IL-18 also modulates Th2 and Th17 cell responses, as well as the activity of CD8 cytotoxic cells and neutrophils, in a host microenvironment-dependent manner. It is produced by various hematopoietic and nonhematopoietic cells, including dendritic cells and macrophages. In an organism, bioactivity of the cytokine depends on the intensity of IL-18 production, the level of its natural inhibitory protein - IL-18BP (IL-18 binding protein) and the surface expression of IL-18 receptors (IL-18R) on the responding cells. This review summarizes the biology of the IL-18/IL-18BP/IL-18R system and its role in the host defense against infections. The prospects for IL-18 application in immunotherapeutic or prophylactic interventions in infectious and non-infectious diseases are discussed.

Neurological associations of SARS-CoV-2 infection: A Systematic Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Amaan Javed
Keyword(s):  
Systematic Review ◽  
Case Reports ◽  
Case Series ◽  
Severe Infection ◽  
Cerebrovascular Diseases ◽  
Controlled Vocabulary ◽  
Cochrane Central Register ◽  
Post Traumatic Stress ◽  
Medical Subject Headings ◽  
Reported Data

Background: The current ongoing COVID-19 pandemic has compelled us to scrutinize major outbreaks in the past two decades, severe acute respiratory syndrome (SARS), in 2002, and Middle East respiratory syndrome (MERS), in 2012. We aimed to assess the associated neurological manifestations with SARS CoV-2 infection. Methods: In this systematic review, a search was carried out by key-electronic databases, controlled vocabulary, and indexing of trials to evaluate the available pertinent studies which included both medical subject headings (MeSH) and advance electronic databases comprising of PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL). Peer-reviewed studies published in English and Spanish were considered which reported data on the neurological associations of individuals with suspected or laboratory-confirmed SARS-CoV-2 infection. Outcomes were nervous signs or symptoms; symptom severity; and diagnoses. Findings: Our search identified 45 relevant studies, with 21 case reports, 3 case series, 9 observational studies, 1 retrospective study, 9 retrospective reviews, and 2 prospective reviews. This systematic review revealed that most commonly reported neuronal presentations involved headache, nausea, vomiting and muscular symptoms like fibromyalgia. Anosmia and ageusia, defects in clarity or sharpness of vision (error in visual acuity), and pain may occur in parallel. Notable afflictions in the form of anxiety, anger, confusion, post-traumatic stress symptoms, and post-intensive care syndrome were observed in individuals who were kept in quarantine and those with long-stay admissions in healthcare settings. SARS CoV-2 infection may result in cognitive impairment. Patients with more severe infection exhibited uncommon manifestations, such as acute cerebrovascular diseases (intracerebral haemorrhage, stroke), rhabdomyolysis, encephalopathy, Guillain-Barré syndrome. Interpretation: SARS-CoV-2 patients experience neuronal presentations varying with the progression of the infection. Healthcare professionals should be acquainted with the divergent neurological symptoms and to curb misdiagnosis and limit long term sequelae. Health-care planners and policymakers must prepare for this eventuality, while the ongoing studies increase our knowledge base on acute and chronic neurological associations of this pathogen.

scholarly journals APOPTOSIS, MEMORY CELL, AND T-HELPER LYMPHOCYTES BALANCE BETWEEN SEVERE AND MILD BRONCHIAL ASTHMA

2015 ◽  
Vol 21 (4) ◽  
pp. 1-13
Author(s):  
Maha Abd El-wahed ◽  
Ebtesam Ahmed ◽  
Mohamed Mohamed ◽  
Nora Said
Keyword(s):  
Bronchial Asthma ◽  
Memory Cell ◽  
T Helper ◽  
T Helper Lymphocytes ◽  
Mild Bronchial Asthma

Expression of chemokine receptors in the different clinical forms of multiple sclerosis

2002 ◽  
Vol 8 (5) ◽  
pp. 390-395 ◽  
Author(s):  
E M Martínez-Cáceres ◽  
C Espejo ◽  
L Brieva ◽  
I Pericot ◽  
M Tintoré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Receptor Expression ◽  
Membrane Expression ◽  
System A ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Expression Characteristic ◽  
Peripheral Leukocytes

Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS. However, a pattern of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.

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