Dendritic Cells in Hepatitis C Virus Infection

Background: The global prevalence of chronic hepatitis C is estimated at 2.8%. There is markedly higher prevalence in the Middle East about 14.7% in Egypt. Dendritic cells (DCs) are one of the major Antigen presenting cells in the body. They bridge innate and adaptive immunity and impact priming of HCVspecific immune responses. The current study was aimed to investigate the DC activation status, and their role in interaction with natural killer (NK) cells utilizing different setups with healthy NK and HCV+ DC, HCV+ NK and healthy DC, healthy DC and healthy NK and finally HCV+ NK and HCV+ DC in the presence of HCV peptides and a ratio of 5 NK: 1DC. Results: DC-NK interaction in chronic HCV infection is mainly affected by the affection of DCs by HCV leading to a maturation defect (decreased expression of HLA DR, CD 86 and CD 83). Healthy NK cells were able to stimulate the maturation of DCs particularly with core peptide whereas NS3-4 had no effect. When DCs were healthy, all peptides were able to produce significant maturation of DCs even when cocultured with HCV+ NK cells. Co-cultured HCV+ NK cells and HCV+ DCs showed significantly higher apoptosis of both cells. This could be attributed to the immature moDCs more with chronic HCV infection due to the fact that immature DCs typically under express HLA-class I molecules that would protect from NK-mediated lysis. Conclusion: Cross-talk between DCs and NK cells plays an important role in the induction of both the innate and adaptive immune systems. HCV infection was found to impair the maturation of DCs. Thus consequently affecting its antigen presentation and T cell allostimulatory capacity and rendering them more liable to NK mediated lysis which could explain the persistence of infection and chronicity

Serum indolamine 2,3 dioxygenase as a marker in the evaluation of allergic rhinitis.

BACKGROUND: Allergic rhinitis occurs on exposure to a known allergen and is correlated with a positive skin test and physical examination results. Tryptophan is a substrate of many important proteins, e.g., indolamine 2,3 dioxygenase (IDO). IDO, an immunomodulator, is a metabolic enzyme induced by immune activation. It has a significant role in allergic reactions. T-helper 2 cell is proposed to affect the expression of IDO. AIM: To evaluate IDO levels in patients with allergic rhinitis compared with controls and its relationship to the severity of allergic rhinitis. METHODS: This case-control study included 20 patients who were atopic and with allergic rhinitis who attended the allergy clinic of Ain Shams University Hospitals. Twenty age- and sex-matched patients who were not atopic were included as controls. An allergic rhinitis diagnosis was made according to the Allergic Rhinitis and its Impact on Asthma document. Complete history taking, physical examination, skin-prick test, complete blood cell count, erythrocyte sedimentation rate, total serum immunoglobulin E (IgE), IDO concentration, and nasal smear for eosinophils were done for the patients. RESULTS: There was a significant increase in IDO levels in allergic rhinitis in comparison with subjects without allergy (p < 0.001). IDO was positively correlated with total IgE levels (p < 0.037). There was an insignificant relationship among IDO levels and age, sex, duration of the disease, severity score, nasal and blood eosinophilia, and number of positive allergens. CONCLUSION: IDO plays an important role in patients with atopic symptomatic allergic rhinitis, especially with increased levels of IgE. There is no relationship between IDO levels and severity of disease.

Comparison between magnetic activated cell sorted monocytes and monocyte adherence techniques for in vitro generation of immature dendritic cells: an Egyptian trial.

INTRODUCTION: Dendritic cells (DCs) are the most efficient antigen presenting cells, which are considered a central component of the immune system for their extraordinary capacity to initiate and modulate the immune responses elicited upon recognition of infectious agents. This has made them a major focus of interest in the conception of immunotherapeutic vaccine strategies. AIM OF THE STUDY: To standardise a protocol for in vitro differentiation of human peripheral blood monocytes into immature DCs (iDCs) upon treatment with specific growth factors and to compare two monocyte isolation methods including magnetic activated cell sorted (MACS) monocytes by CD14(+) immuno-magnetic beads and monocytes separated by adherence. MATERIAL AND METHODS: Immature DCs were generated from monocytes of human peripheral blood in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 after in vitro culture for seven days. Cultured cells were stained with surface markers of iDCs: FITC-anti-CD14, PE-anti-CD11c, PE-anti-CD1a, PE-Cy5-anti-HLA-DR, and PE-anti-CD83 for flow cytometry analysis. RESULTS: We found that the viability of MACS-DCs was higher than DCs derived from monocytes separated by adherence (median 50 and interquartile range 45-50 vs. 25 and 10-30, respectively; p < 0.001). Flow cytometry analysis revealed that the median interquartile percentages of MACS-DCs expressing CD14(-) was significantly higher compared to the DCs derived from monocytes separated by adherence (median 80.2 and interquartile range 77.7-80.7 vs. 40.2 and 30.4-40.6, respectively; p < 0.001). However, MACS-DCs expressed the same levels of CD11c, CD1a, and HLA-DR as well as CD83 compared to the DCs derived from monocytes separated by adherence with p value > 0.05. CONCLUSIONS: Both positively selected monocytes and monocytes separated by adherence procedure gave the same results as regards cell surface marker expression, although the DCs purity and viability using MACS separated monocytes were better.

OX40 ligand: a potential costimulatory molecule in atopic asthma.

OBJECTIVE: We aimed to assess the percentage of peripheral blood B-lymphocytes expressing OX40 ligand (OX40L) in adult atopic and non-atopic asthmatic patients, and in healthy controls. METHODS: This case-control study included 15 atopic asthmatic patients, 15 non-atopic asthmatic patients, and 15 healthy controls. Atopic status was determined by skin prick test reaction to the most common locally-encountered allergens. For all subjects, pulmonary function tests and measurement of total serum immunoglobulin E (IgE) levels by ELISA were performed. In addition, the percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry in all three groups. RESULTS: OX40L expression was significantly higher in atopic asthmatics than in non-atopic asthmatics and controls, but did not differ significantly between non-atopic asthmatics or controls. Among atopic asthmatics, OX40L expression correlated positively with total serum IgE levels, but not with age, disease duration, or values of forced expiratory volume in the first second. CONCLUSION: The over-expression of OX40L in atopic asthmatic patients appears to be linked to markers of the atopic status as total serum IgE, and signifies the vital role of OX40L in the atopic mechanism. Further large-scale studies are needed to investigate the role of OX40L in other atopic diseases and its relation to disease activity and severity.