Hungarian Immunology

[Extensive flow cytometric characterization of plasmocytoid dendritic cell leukemia cells]

GOPCSA László, KORMOS Luca, BÁNYAI Anikó, TAMÁSKA Júlia, MATOLCSY András, GOGOLÁK Péter, RAJNAVÖLGYI Éva, PÁLÓCZI Katalin

OCTOBER 10, 2005

Hungarian Immunology - 2005;4(03-04)

[INTRODUCTION - Accumulating evidences suggest that non-T, non-B cell CD4+/CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. CASE REPORT - In this work we present the immunophenotypic and genotypic features of bone marrow, peripheral blood, lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, bone marrow, peripheral blood, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation and co-stimulatory molecules were used. The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2 and granzyme-B corresponding to the preplasmacitoid dendritic cell developmental stage. CONCLUSION - The presence of CD11a/CD18, CD84, CD91, CD95, αvβ5, CDw197 and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells.]

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MAGYARICS Zoltán, RAJNAVÖLGYI Éva

[Dendritic cells represent a multifunctional cell population classified to myeloid (mDC) and plasmacytoid (pDC) types. Both subsets circulate in the peripheral blood and are found in lymphoid and also in non-lymphoid tissues, where they act as sensors of environmental changes. Upon activation by a wide range of stimuli they undergo morphological and functional transition and give rise to professional antigen presenting cells, which migrate to lymphoid organs. A newly identified precursor subset of human dendritic cells has recently been identified as professional type I interferon producing cells (IPC) with multiple functional activities. With their capacity of priming, instructing and regulating various pathogen- and tumor-specific immune responses, IPC/pDC act as a link between innate and adaptive immunity. The role of pDC in the pathogenesis of various diseases is well established, and these cells also emerge as novel candidates of immunomodulation.]

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[INTRODUCTION - CD4+/CD25+high suppressor and IL-10 producing CD4+ regulatory T (IL-10 Treg) cells were investigated in the peripheral blood of 48 patients with mixed connective tissue disease (MCTD). Seventeen patients were in active and 31 patients in inactive state. PATIENTS AND METHODS - Measurement of the number of CD4+CD25+high suppressor and IL-10 Treg cells was carried out by flow cytometry. RESULTS - The absolute number and percent of CD4+CD25+high T cells decreased in MCTD patients compared to the healthy controls. The number of CD4+CD25+high Treg cells was lower in 17 active MCTD patients than in the inactive patients. The percent and absolute number of IL-10 Treg was elevated in the peripheral blood of patients with MCTD compared to the healthy controls. Corticosteroid and immunosuppressive drugs moved the number of regulatory T cells (CD4+CD25+high and IL-10 Treg cells) towards the normal value. CONCLUSIONS - Our results show that the decrease in the number of CD4+CD25+high T cells could play a key role in the immunoregulatory disturbance in MCTD. Elevation in the number of IL-10 Treg cells might be a compensatory mechanism to retain the balance of proinflammatory and anti-inflammatory cytokines.]

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[INTRODUCTION - The treatment of pediatric leukemia has become increasingly successful, with a survival rate over 80%. Thus interest has been increasingly focused on the long-term side-effects of the treatment. The questions of reduced fertility rate, occurance of second malignancies, cardiomyopathy, impaired renal and pulmonal function have been extensively studied. Changes of bone metabolism in connection with the disease itself and the treatment have been analysed in the past decade. CASE REPORT - We present the case of a 15-year-old boy with acute lymphoblastic leukemia, who had bone pain soon after the diagnosis. During the course of chemotherapy his complaints were fluctuating, and he developed severe osteoporosis. The level of a bone resorption marker, β-CrossLaps, was elevated. In the second year of therapy an acute pain of the left hip occured with fever and restriction of joint movement, which was diagnosed and treated as osteomyelitis. A few months later avascular necrosis of the left femoral head was revealed. Both pharmaceutic (calcium, vitamin D, calcitonin, bisphophonate) and orthopedic treatment were used, as a result bone mineral density and movement restriction improved; his leukemia is now in remission. CONCLUSIONS - The factors influencing bone metabolism in leukemic children are reviewed. Firstly the effects of malignant cells on bone mineral content are analyzed, then the chemotherapeutic drugs’ mechanisms of action are examined extensively. The direct and indirect effects of secondary factors (hospitalization, immobility, lack of sun exposure, malabsorption, immunsuppression, peripheral neuropahty) are also analyzed. The advantages and disadvantages of drugs used in preventing and treating childhood osteopenia are reviewed.]

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[Investigation of activated T-cells by non-Hodgkin’s lymphoma patients]

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[BACKGROUND - The immune system has several mechanisms to fight against developing malignant cell clones in the host, one of them is the activated T-cell response. Both CD4+ helper and CD8+ cytotoxic T-cells bear CD69 and HLA-DR molecules as important surface activation markers. AIM - Our aim was to determine, how the ratio of activated T-cells change in the peripheral blood of non-Hodgkin-lymphoma patients during the periods of polychemotherapy. PATIENTS AND METHODS - We used the peripheral blood samples of 43 non-Hodgkin-lymphoma’s patients (20 females, 23 males, mean age 52.4 years). We determined the level of CD3+/HLADR+ and CD3+/CD69+ T-cell subsets before, during and after the periods of polychemotherapy, using the methods of immunofluorescence stain and flow cytometry. RESULTS - We found the ratio of CD3+/HLA-DR+ cells significantly higher in non-Hodgkin-lymphoma’s patients before treatment compared to healthy controls (10.63% vs. 2.97%, p<0.001). During the period of polychemotherapy, this ratio began to increase significantly (16.94% vs. 10.63%, p=0.006). The level of CD3+/CD69+ cells did not change significantly. After treatment, the ratio of activated T-cells decreased, however, we detected significantly higher rate of CD3+/HLA-DR+ lymphocytes in patients who relapsed within one year than in those who stayed in remission (9.55% vs. 20.62%, p<0.001). CONCLUSION - Investigation of CD3+/HLA-DR+ activated T-cells might be a promising method to determine the immune defence and this way the prognostics of lymphoma patients.]

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[Normal functions of the cell are based on the precise regulation of various genes. If this strict regulation and the hierarchy of genes becomes upset due to some flaws of the system, the result will be cellular dysfunction which may eventually lead to carcinogenic transformation. The two main challenges in the classification of cancers are the discovery of new molecular markers characteristic to defined disease groups and the classification of already diagnosed or new cases into existing groups. This precise classification may open the door to tailored treatment or project the expected outcome of the disease. Today, there is unlimited access available to the databases containing sequences and localisation of the genes within the confines of Human Genome project. It provides significant help for the discovery of chromosome abnormalities and systematic analysis of gene expression patterns. This is important not only to understand normal functions of the cells, but it also contributes to the identification of new genes that are characteristic to given disease groups as markers and that are potential drug targets. Until the second half of the twentieth century the study of the function and regulation of genes was based on step by step investigation of individual genes. The fact that the genomes of an increasing number of organisms have become identified in whole or in part, numerous new techniques have been developed facilitating the systematic analysis of gene functions. The aim of this study is to summarise the new, molecular based possibilities for classification, diagnosis and prognosis of cancers, as well as to summarise the results of these areas, primarily from the point of view of leukemias.]

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[INTRODUCTION - IL-6 is a multifunctional cytokine with effects on the haematopoiesis on differentiation of T and B lymphocytes and on the regulation of both inflammatory and allergic reactions. The question arose whether this substance excreted by mononuclear cells could be used as a marker of allergy to drugs or not. Till now equivocal descriptions were lacking. METHOD - The preformed IL-6 present in the mononuclear cells released by any of four standard dilutions of pure substances upon 20 minutes incubation was determined from the supernatants by ELISA technique. In vivo patch, intradermal and provocation tests were carried out along with this assay (483 in vitro and 172 in vivo). RESULTS - Two different groups suspect for drug allergy (100 and 62 patients as well as their matching controls, 24 and 23 persons) were involved with these procedures. In some cases TNF-α, IL-2, IFN-γ and IL-4 was measured simultaneously by flow cytometric assay. Only TNF-α and IL-6 were present in the 20 min. supernatants. The comparisons with in vivo tests have confirmed that the amount of IL-6 release had not depended either on the clinical phenotype of allergy or on the structure of the tested drugs within the molecular mass range between 76-4000 Da. IL-6 released at the lowest or multiple concentrations of drugs coincided with more severe and widespread clinical forms. CONCLUSION - Based on the results we elaborated an in vitro method applicable clinically for detecting drug sensitisation and its differential diagnosis in patients with skin signs of drug sensitisation.]