scholarly journals Genetic and immune-toxicologic studies on abnormal thyroid functions in hospital employees exposed to cytostatic drugs

2015 ◽  
Vol 156 (2) ◽  
pp. 60-66
Author(s):  
Anna Tompa ◽  
Mátyás Jakab ◽  
Anna Biró ◽  
Jenő Major
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chromosome Aberrations ◽  
Cytotoxic T Cells ◽  
Reactive Oxygen ◽  
Neutrophil Granulocytes ◽  
Pathophysiological Mechanism ◽  
Cytostatic Drugs ◽  
Oxygen Intermediates ◽  
Occupationally Exposed

Introduction: Environmental exposure to harmful chemicals may produce severe consequences. Aim: The aim of the authors was to perform geno- and immune-toxicological monitoring in female employees occupationally exposed to cytostatic agents in hospitals and compare the findings to those obtained from controls. Method: Altogether 642 women working in hospital who were occupationally exposed to cytostatic drugs and 262 control women participated in the study. Frequency of chromosome aberrations, immune phenotype and activation of lymphocytes, and the production of reactive oxygen-species in neutrophil granulocytes were determined. Results: Markedly higher number (n=39) of thyroid alterations was observed among exposed subjects as compared to controls (n=3). In persons with abnormal thyroid functions, the frequency of chromosome aberrations (3.69%) was significantly higher (3.69%) than in exposed subjects without thyroid alterations (2.43%) and in controls (1.70% and 1.60% in control subjects with and without thyroid alterations, respectively). Significantly increased ratio of helper T lymphocytes and decreased ratio of cytotoxic T cells and transferrin-receptor (CD71) expressing B cells were observed in exposed subjects having abnormal thyroid functions as compared to controls. In addition, the ratio of B cells, CD71 expressing T cells and production of reactive oxygen-intermediates was significantly decreased in exposed subjects with thyroid alterations in comparison to exposed subjects without thyroid alterations. Conclusions: The results indicate increased geno- and immune-toxic effects among exposed subjects having thyroid alterations. Further data are needed to clearly establish the underlying pathophysiological mechanism of this finding. Orv. Hetil., 2015, 156(2), 60–66.

scholarly journals Selective Induction of Th2-Attracting Chemokines CCL17 and CCL22 in Human B Cells by Latent Membrane Protein 1 of Epstein-Barr Virus

2004 ◽  
Vol 78 (4) ◽  
pp. 1665-1674 ◽  
Author(s):  
Takashi Nakayama ◽  
Kunio Hieshima ◽  
Daisuke Nagakubo ◽  
Emiko Sato ◽  
Masahiro Nakayama ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Epstein Barr Virus ◽  
Cytotoxic T Cells ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT Chemokines are likely to play important roles in the pathophysiology of diseases associated with Epstein-Barr virus (EBV). Here, we have analyzed the repertoire of chemokines expressed by EBV-infected B cells. EBV infection of B cells induced expression of TARC/CCL17 and MDC/CCL22, which are known to attract Th2 cells and regulatory T cells via CCR4, and also upregulated constitutive expression of MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5, which are known to attract Th1 cells and cytotoxic T cells via CCR5. Accordingly, EBV-immortalized B cells secreted these chemokines, especially CCL3, CCL4, and CCL22, in large quantities. EBV infection or stable expression of LMP1 also induced CCL17 and CCL22 in a B-cell line, BJAB. The inhibitors of the TRAF/NF-κB pathway (BAY11-7082) and the p38/ATF2 pathway (SB202190) selectively suppressed the expression of CCL17 and CCL22 in EBV-immortalized B cells and BJAB-LMP1. Consistently, transient-transfection assays using CCL22 promoter-reporter constructs demonstrated that two NF-κB sites and a single AP-1 site were involved in the activation of the CCL22 promoter by LMP1. Finally, serum CCL22 levels were significantly elevated in infectious mononucleosis. Collectively, LMP1 induces CCL17 and CCL22 in EBV-infected B cells via activation of NF-κB and probably ATF2. Production of CCL17 and CCL22, which attract Th2 and regulatory T cells, may help EBV-infected B cells evade immune surveillance by Th1 cells. However, the concomitant production of CCL3, CCL4, and CCL5 by EBV-infected B cells may eventually attract Th1 cells and cytotoxic T cells, leading to elimination of EBV-infected B cells at latency III and to selection of those with limited expression of latent genes.

scholarly journals P2.03-37 The Efficiency of Octamer-4 Specific Cytotoxic T Cells Induce By CD40-B Cells in Killing Lung Cancer Stem-Like Cells

2018 ◽  
Vol 13 (10) ◽  
pp. S730
Author(s):  
X. Zhang ◽  
J. Xu ◽  
F. Hu ◽  
H. Wang ◽  
X. Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells

scholarly journals New insights in the biology of Hodgkin lymphoma

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 328-334 ◽  
Author(s):  
Ralf Küppers
Keyword(s):  
T Cells ◽  
B Cells ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Cell Gene Expression ◽  
Expression Program ◽  
Multiple Signaling ◽  
Cell Gene

Abstract The Hodgkin and Reed/Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (HL) and the lymphocyte-predominant tumor cells of nodular lymphocyte–predominant HL are both derived from germinal center B cells. HRS cells, however, have largely lost their B-cell gene-expression program and coexpress genes typical of various types of hematopoietic cells. Multiple signaling pathways show a deregulated activity in HRS cells. The genetic lesions involved in the pathogenesis of HL are only partly known, but numerous members and regulators of the NF-κB and JAK/STAT signaling pathways are affected, suggesting an important role for these pathways in HL pathogenesis. Some genetic lesions involve epigenetic regulators, and there is emerging evidence that HRS cells have undergone extensive epigenetic alterations compared with normal B cells. HRS and lymphocyte-predominant cells are usually rare in the lymphoma tissue, and interactions with other cells in the microenvironment are likely critical for HL pathophysiology. T cells represent a main population of infiltrating cells, and it appears that HRS cells both inhibit cytotoxic T cells efficiently and also receive survival signals from Th cells in direct contact with them.

scholarly journals Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes.

1993 ◽  
Vol 177 (6) ◽  
pp. 1821-1826 ◽  
Author(s):  
T J Schall ◽  
K Bacon ◽  
R D Camp ◽  
J W Kaspari ◽  
D V Goeddel
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Human Macrophage ◽  
Immune Effector ◽  
Effector Cells ◽  
Inflammatory Protein ◽  
And Migration ◽  
Macrophage Inflammatory Protein

Lymphocyte trafficking is an essential process in immune and inflammatory functions which can be thought to contain at least two main components: adhesion and migration. Whereas adhesion molecules such as the selections are known to mediate the homing of leukocytes from the blood to the endothelium, the chemoattractant substances responsible for the migration of specific subsets of lymphocytes to sites of infection or inflammation are largely unknown. Here we show that two molecules in the chemokine (for chemoattractant cytokine) superfamily, human macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta, do not share identical attractant activities for lymphocyte subpopulations. When analyzed in vitro in microchemotaxis experiments, HuMIP-1 beta tends to attract CD4+ T lymphocytes, with some preference for T cells of the naive (CD45RA) phenotype. HuMIP-1 alpha, when tested in parallel with HuMIP-1 beta, is a more potent lymphocyte chemoattractant with a broader range of concentration-dependent chemoattractant specificities. HuMIP-1 alpha at a concentration of 100 pg/ml attracts B cells and cytotoxic T cells, whereas at higher concentrations (10 ng/ml), the migration of these cells appears diminished, and the migration of CD4+ T cells is enhanced. Thus, in this assay system, HuMIP-1 alpha and -1 beta have differential attractant activities for subsets of immune effector cells, with HuMIP-1 alpha having greater effects than HuMIP-1 beta, particularly on B cells.

scholarly journals Efficient Generation of Antigen-Specific Cytotoxic T Cells Using Retrovirally Transduced CD40-Activated B Cells

2002 ◽  
Vol 169 (4) ◽  
pp. 2164-2171 ◽  
Author(s):  
Eisei Kondo ◽  
Max S. Topp ◽  
Hans-Peter Kiem ◽  
Yuichi Obata ◽  
Yasuo Morishima ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Efficient Generation ◽  
Activated B Cells

scholarly journals Reactive lymphocytes in lacrimal gland and vasculitic renal lesions of autoimmune MRL/lpr mice express L3T4.

1987 ◽  
Vol 166 (4) ◽  
pp. 1198-1203 ◽  
Author(s):  
D A Jabs ◽  
R A Prendergast
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lacrimal Gland ◽  
Lymphocyte Subsets ◽  
Cytotoxic T Cells ◽  
Immunologic Response ◽  
Inflammatory Lesions ◽  
Renal Lesions ◽  
Renal Vasculitis ◽  
Reactive Lymphocytes

The lacrimal gland inflammatory lesions and renal vasculitic lesions of autoimmune MRL/lpr mice were analyzed for the lymphocyte subsets present. The majority of cells were Thy-1.2+ T cells (mean, 85%) of the L3T4+ helper T phenotype (mean, 64 and 58%, respectively). Lesser numbers of Lyt-2+ suppressor/cytotoxic T cells, B cells, and macrophages were present. The finding that the majority of lymphocytes in both the lacrimal gland inflammatory lesions and renal vasculitis of MRL/lpr mice expressed L3T4 suggests that these cells may be capable of responding to antigen presentation and that an active immunologic response occurs at these sites.

Increased Number of B-Cells In the Red Pulp of the Spleen In ITP

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1447-1447
Author(s):  
Bob Olsson ◽  
Hans Wadenvik ◽  
Margareta Jernås ◽  
Börje Ridell
Keyword(s):  
T Cells ◽  
Platelet Count ◽  
B Cells ◽  
Lymphocyte Subsets ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Splenic Tissue ◽  
White Pulp ◽  
Chronic Itp ◽  
Red Pulp

Abstract Abstract 1447 Background. Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system, e.g. the spleen, in patients with chronic immune thrombocytopenia (ITP). However, other pathophysiologic mechanisms such as platelet destruction by cytotoxic T-cells and defective bone marrow production of platelets also contribute to the thrombocytopenia in ITP. Splenectomy normalizes the platelet count in around 70% of chronic ITP patients, however, precious little is known about the spleen micromorphology in this disease. We examined splenic pathology in patients with ITP, focusing on the intrasplenic distribution of lymphocyte subsets. Patients and Methods. The paraffin-embedded block containing representative material of the splenic tissue from 29 splenectomized chronic ITP patients (15 females and 14 males, mean age 45±21 (SD) years) and 11 controls, splenectomized because of traumatic splenic rupture (2 females and 9 males, mean age 48±19 (SD) years), was used to produce serial sections with a thickness of 5 μm. These sections were stained with conventional haematoxylin-eosin, and immunostained to identify CD3, CD4, CD8, CD20 and CD68 using the Dako Envision System in a Techmate Horizon Autostainer (Glostrup, Denmark). Using micromorphometry the lymphocyte subsets were enumerated in the red and white pulp of these spleens. Results. All ITP patients were preoperatively optimized, using corticosteroids and/or IVIg, and the immediate pre-splenectomy platelet count ranged 5–357 × 109/l. Significantly more T-cells than B-cells were seen in the red pulp, both in ITP and control spleens (p<0.01). Conversely, more B-cells than T-cells were observed in the white pulp. There was no difference in the number of T-cells in the red and white pulp, between ITP patients and controls. However, the number of B-cells was increased in the red pulp of patients with ITP compared with the controls. Furthermore, numerous B-cells and CD8+ (cytotoxic) T-cells were located in the splenic cords, lining the sinusoids in the red pulp, a microenvironment where they readily can interact with the other blood cells, e.g. platelets. Conclusion. Chronic ITP is associated with an increased number of CD20+ B-cells in the red pulp of the spleen. The red pulp of the spleen also provides a microenvironment where close interaction between platelets, CD3+, CD4+, and CD8+ T-cells and B-cells can take place. Trafficking of regulatory and effector cells into this microenvironment might be a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD95-CD95L interaction mediates the growth control of MHV68 immortalized B cells by cytotoxic T cells

2017 ◽  
Vol 32 (3) ◽  
pp. 257-259
Author(s):  
Sihan Dong ◽  
Lingbing Tan ◽  
Guifang Chen ◽  
Xiaozhen Liang
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Growth Control

scholarly journals Immunomodulatory activities of non-commercialized leafy vegetables in KwaZulu-Natal, South Africa

2012 ◽  
Author(s):  
◽  
Berushka Padayachee
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Leafy Vegetables ◽  
Aqueous Extracts ◽  
Immune Functions ◽  
Bidens Pilosa ◽  
Methanolic Extracts ◽  
Ifn Γ ◽  
Asystasia Gangetica

Immunomodulation using plants is of primary interest in scientific communities because it provides an alternative to conventional chemotherapy for a wide range of diseases. It is based on the ability of the plants to effectively modulate immune functions, thus being able to promote positive health and maintain the body’s resistance to infection. This research is aimed to evaluate the immunomodulatory potential of fourteen traditional leafy vegetables from Kwa-Zulu Natal, South Africa on human peripheral blood mononuclear cells (PBMC). In this study the methanolic and aqueous extracts were screened for lymphocyte proliferation using the MTT assay. The cytokine response was evaluated by measuring the secretion of interleukin 10 (IL-10) and interferon-gamma (IFN-γ) using the ELISA assay. The subpopulation of T cells viz., CD4+, CD8+, NK and B cells were measured by flow cytometry. Most of the methanolic extracts stimulated PBMC’s whilst a few suppressed lymphocyte proliferation. Most of the aqueous extracts were inactive. The methanolic extracts of Amaranthus hybridus and Centella asiatica stimulated PBMC’s and showed an increase in IFN-γ secretion and the CD8+ cytotoxic T cells and B cells. Thus, they induced the Tc-1 immune response and stimulated cell mediated immunity. The methanolic extracts of Asystasia gangetica, Bidens pilosa, Emex australis, Justicia flava Momordica balsamina, Oxygonum sinuatum, Senna occidentalis and Sonchus oleraceous and the aqueous extracts of Amaranthus spinosus and Asystasia gangetica, Ceratotheca triloba, Oxygonum sinuatum, Physalis viscosa and Sonchus oleaceous stimulated PBMC’s and showed an increase in IL-10 secretion and the CD8+ cytotoxic T cells and B cells. Thus, they induced the Tc-2 immune response and stimulated humoral immunity. Also, the methanolic extracts of Amaranthus spinosus and Ceratotheca triloba and the aqueous extracts of Bidens pilosa and Justicia flava increased both IL-10 and IFN-γ secretion and the CD8+ vii cytotoxic T cells indicating the stimulation of both the Tc1 and Tc2 cytokine profiles. The elevated secretion of IFN-γ and IL-10 caused by the extracts can be attributed to the CD8+ cytotoxic T cells and B cells. The findings of this study show that leafy vegetables hold promise as immunomodulatory candidates. They may enhance cell-mediated immune functions by a pro-inflammatory response whilst some can promote humoral immune functions by means of an anti-inflammatory response. Further investigation should be considered on the effect of the extracts on other immune parameters.

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