Recruitment of circulating dendritic cell precursors into the infarcted myocardium and pro-inflammatory response in acute myocardial infarction

2012 ◽  
Vol 123 (6) ◽  
pp. 387-398 ◽  
Author(s):  
Daniel Kretzschmar ◽  
Stefan Betge ◽  
Alexander Windisch ◽  
Rudin Pistulli ◽  
Ilonka Rohm ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Myeloid Dendritic Cells ◽  
Peripheral Tissues ◽  
Infarcted Myocardium

DC (dendritic cells) play an important role in the immune system. They invade peripheral tissues to detect harmful antigens, inducing a local immune response. Studies suggest that DCPs (dendritic cell precursors) might be reduced in AMI (acute myocardial infarction); however, the reason for their reduction is unknown yet. In the present study, circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs), tDCPs (total DCPs) and serum levels of TNFα (tumour necrosis factor α), IL (interleukin)-2, -4, -5, -6, -10 and -12 were analysed by flow cytometry in blood of patients with NSTEMI [non-STEMI (ST-segment elevation myocardial infarction)] (n=44) and STEMI (n=34) compared with controls with excluded CAD (coronary artery disease) (n=45). Post-mortem myocardial specimens of patients with AMI (n=12) and healthy myocardium of accident victims (n=10) were immunostained for mDCs (myeloid dendritic cells) T-cells and macrophages. Compared with controls, in patients with AMI a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.0001). The extent of the decrease was higher in STEMI than NSTEMI patients. Serum levels were significantly higher in patients with AMI compared with controls for IL-6, -10, -12 and TNFα (each P<0.03). Immunostaining revealed significantly higher number of DCs, T-cells and macrophages (each P<0.002) in infarcted than control myocardium. We show that circulating DCPs are significantly reduced in AMI, with a pronounced reduction in STEMI patients. This was accompanied by a significant increase of inflammatory serum cytokines in patients with AMI. Immunohistochemical analysis unravelled that the reduction of circulating DCPs might be due to recruitment into the infarcted myocardium.

Sézary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3287-3294 ◽  
Author(s):  
Maria Wysocka ◽  
Mohamed H. Zaki ◽  
Lars E. French ◽  
Jihed Chehimi ◽  
Michael Shapiro ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Tumor Burden ◽  
Cell Mediated Immunity ◽  
Ifn Γ ◽  
Malignant T Cells

Abstract Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma associated with involvement of the peripheral blood by malignant T cells. The disease is defined by impaired cell-mediated immunity and the production of interferon-γ (IFN-γ) and interleukin-2 (IL-2), possibly as a result of deficient IL-12 production. To understand the mechanism of this impairment, we examined the composition and function of dendritic cells and monocytes in the blood of SzS patients with different levels of peripheral blood tumor burden. Consistent with our previous observations, numbers of monocytes in SzS patients were comparable to numbers observed in healthy donors. In contrast, decreased IL-12 production correlated with a decrease in the numbers of CD11c+ dendritic cells, which was particularly profound among patients with medium (20%-50% circulating malignant T cells) and high (more than 50% circulating malignant T cells) tumor burden. Furthermore, CD123+ dendritic cells, major producers of IFN-α, were significantly diminished in SzS patients, regardless of the level of tumor burden. Granulocyte macrophage–colony-stimulating factor–treated patients experienced an increase in the number of dendritic cells but not in IFN-α or IL-12 production. However, in vitro stimulation of peripheral blood mononuclear cells from SzS patients with rCD40L and IFN-γ significantly increased the production of IL-12. Thus, our results demonstrate a profound defect in circulating dendritic cells in SzS patients that may contribute to the pathogenesis of the cytokine disorders and to the depressed cellular immunity. Importantly, the ability of rCD40L to potently induce IL-12 production from monocytes and residual dendritic cells of SzS patients could potentially serve as an immune-restorative therapeutic agent.

scholarly journals Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2655-2661 ◽  
Author(s):  
Devi K. Banerjee ◽  
Madhav V. Dhodapkar ◽  
Elyana Matayeva ◽  
Ralph M. Steinman ◽  
Kavita M. Dhodapkar
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Interleukin 2 ◽  
Cell Contact ◽  
Myeloid Dendritic Cells ◽  
Healthy Donors

AbstractCD4+CD25+FOXP3+ regulatory T cells (Treg's) play an important role in the maintenance of immune tolerance. The mechanisms controlling the induction and maintenance of Treg's in humans need to be defined. We find that human myeloid dendritic cells (DCs) are superior to other antigen presenting cells for the maintenance of FOXP3+ Treg's in culture. Coculture of DCs with autologous T cells leads to an increase in both the number of Treg's, as well as the expression of FOXP3 protein per cell both in healthy donors and myeloma patients. DC-mediated expansion of FOXP3high Treg's is enhanced by endogenous but not exogenous interleukin-2 (IL-2), and DC-T-cell contact, including the CD80/CD86 membrane costimulatory molecules. DCs also stimulate the formation of Treg's from CD25- T cells. The efficacy of induction of Treg's by DCs depends on the nature of the DC maturation stimulus, with inflammatory cytokine-treated DCs (Cyt-DCs) being the most effective Treg inducers. DC-induced Treg's from both healthy donors and patients with myeloma are functional and effectively suppress T-cell responses. A single injection of cytokine-matured DCs led to rapid enhancement of FOXP3+ Treg's in vivo in 3 of 3 myeloma patients. These data reveal a role for DCs in increasing the number of functional FOXP3high Treg's in humans.

scholarly journals Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Zhipeng Zeng ◽  
Kunwu Yu ◽  
Long Chen ◽  
Weihua Li ◽  
Hong Xiao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Interleukin 2 ◽  
Treg Cells ◽  
Left Ventricular ◽  
Border Zone ◽  
Infarcted Myocardium

CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV) function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th) cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

scholarly journals CD1d on Myeloid Dendritic Cells Stimulates Cytokine Secretion from and Cytolytic Activity of Vα24JαQ T Cells: A Feedback Mechanism for Immune Regulation

2000 ◽  
Vol 165 (7) ◽  
pp. 3756-3762 ◽  
Author(s):  
Otto O. Yang ◽  
Frederick K. Racke ◽  
Phuong Thi Nguyen ◽  
Rudolf Gausling ◽  
Michael E. Severino ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Regulation ◽  
Feedback Mechanism ◽  
Cytolytic Activity ◽  
Cytokine Secretion ◽  
Myeloid Dendritic Cells

scholarly journals Murine Myeloid Dendritic Cells That Phagocytose Apoptotic T Cells Inhibit the Immune Response via NO

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49378 ◽  
Author(s):  
Kaili Zhong ◽  
Wengang Song ◽  
Qian Wang ◽  
Chao Wang ◽  
Xi Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Myeloid Dendritic Cells

Variations in serum T3, rT3, 3,3'-diiodothyronine and 3',5'-diiodothyronine induced by acute myocardial infarction and propranolol

1980 ◽  
Vol 94 (3) ◽  
pp. 341-345 ◽  
Author(s):  
Jens Faber ◽  
Carsten Kirkegaard ◽  
Ib Bo Lumholtz ◽  
Kaj Siersbæk-Nielsen ◽  
Thorkild Friis
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Enzyme System ◽  
Serum Levels ◽  
High Serum ◽  
Early Course ◽  
Deiodinase Activity ◽  
Serum T3 ◽  
Low Serum ◽  
Close Parallelism

Abstract. Serum levels of thyroxine, 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2) and TSH were measured in two clinical situations which are both known to induce a low serum T3 high serum rT3 syndrome: 1) during the early course of acute myocardial infarction (AMI) and after recovery, and 2) before and during one week's propranolol medication (20 mg 4 times a day). In 10 patients with AMI serum levels of the iodothyronines were unchanged on admission to hospital (in average 6.6 h after onset of symptoms). However, already 24 h after onset of symptoms serum T3 and 3,3'T2 were reduced whereas serum rT3 and 3',5'-T2 were increased. Serum T3 and 3,3'-T2 reached a nadir on day 4 and 3, respectively, whereas serum rT3 and 3',5'-T2 reached peak values 24 h after onset of symptoms. In eight healthy, euthyroid volunteers propranolol medication induced similar changes in iodothyronine concentration as AMI did. However, the alterations were more delayed. Serum T3 decreased slowly reaching statistically significantly reduced values on day 7. Serum rT3 and 3',5'-T2 were significantly enhanced from day 3 and 4, respectively. A close parallelism in alterations of serum T3 and 3,3'-T2 levels was observed. Our data suggest that T3 in the two situations studied is a major precursor for 3,3'-T2 probably as a consequence of reduced 5'-deiodinase activity. It seems possible that the mechanisms affecting the metabolism of the iodothyronines in AMI and during propranolol medication involved the same enzyme system. However, the late appearance of the alterations in serum iodothyronines levels during propranolol medication might indicate different modes of action.

scholarly journals Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses.

1993 ◽  
Vol 178 (2) ◽  
pp. 633-642 ◽  
Author(s):  
N Bhardwaj ◽  
J W Young ◽  
A J Nisanian ◽  
J Baggers ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Class Ii ◽  
Cell Mediated Immunity ◽  
Quiescent T Cells ◽  
Antigen Presenting

Dendritic cells are potent antigen-presenting cells for several primary immune responses and therefore provide an opportunity for evaluating the amounts of cell-associated antigens that are required for inducing T cell-mediated immunity. Because dendritic cells express very high levels of major histocompatibility complex (MHC) class II products, it has been assumed that high levels of ligands bound to MHC products ("signal one") are needed to stimulate quiescent T cells. Here we describe quantitative aspects underlying the stimulation of human blood T cells by a bacterial superantigen, staphylococcal enterotoxin A (SEA). The advantages of superantigens for quantitative studies of signal one are that these ligands: (a) engage MHC class II and the T cell receptor but do not require processing; (b) are efficiently presented to large numbers of quiescent T cells; and (c) can be pulsed onto dendritic cells before their application to T cells. Thus one can relate amounts of dendritic cell-associated SEA to subsequent lymphocyte stimulation. Using radioiodinated SEA, we noted that dendritic cells can bind 30-200 times more superantigen than B cells and monocytes. Nevertheless, this high SEA binding does not underlie the strong potency of dendritic cells to present antigen to T cells. Dendritic cells can sensitize quiescent T cells, isolated using monoclonals to appropriate CD45R epitopes, after a pulse of SEA that occupies a maximum of 0.1% of surface MHC class II molecules. This corresponds to an average of 2,000 molecules per dendritic cell. At these low doses of bound SEA, monoclonal antibodies to CD3, CD4, and CD28 almost completely block T cell proliferation. In addition to suggesting new roles for MHC class II on dendritic cells, especially the capture and retention of ligands at low external concentrations, the data reveal that primary T cells can generate a response to exceptionally low levels of signal one as long as these are delivered on dendritic cells.

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

scholarly journals CLINICAL STUDY OF ACUTE MYOCARDIAL INFARCTION IN YOUNG ADULTS WITH REFERENCE TO SERUM LIPOPROTEIN, SERUM HOMOCYSTEINE AND HS-CRP

2020 ◽  
pp. 1-3
Author(s):  
Felin Ann Francis
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Elevated Serum ◽  
Young Patients ◽  
Serum Levels ◽  
Serum Lipoprotein ◽  
Considerable Proportion ◽  
Serum Homocysteine ◽  
Younger Generation ◽  
Hs Crp

• Introduction - Recently, the prevalence of acute myocardial infarction (AMI) has been increasing in the younger generation. With the advances in the field of medicine, elevated serum levels of various biomarkers like c-reactive protein (CRP), various lipoproteins and homocysteine have been identified to be related to AMI. • Objective - To clinically diagnose acute myocardial infarction in young patients and correlate the levels of serum lipoprotein, serum homocysteine and serum hs-crp and to calculate the level of risk depending on their levels. • Method - A hospital based observational study in which 50 subjects were enrolled in the study as per the inclusion and exclusion criteria. • Results - The results support the current global findings of the younger generation, especially the males, being affected by AMI (Acute Myocardial Infarction). Sedentary lifestyle and BMI >25 can be considered as major risk factors leading to AMI. A considerable proportion of our AMI patients had significantly elevated levels of homocysteine, hs-CRP and lipoprotein A and low levels of HDL-C indicating their correlation with AMI.

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