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Article
Functional and Developmental Analysis of CD4+CD25+Regulatory T Cells Under the Influence of Streptococcal MProtein in Rheumatic Heart Disease

Author: Zaman I. L. Al-Kaabi
Journal: Iraqi Academic Scientific Journal المجلة العراقية للاختصاصات الطبية ISSN: 16088360 Year: 2012 Volume: 11 Issue: 1 Pages: 76-81
Publisher: The Iraqi Borad for Medical Specialization المجلس العراقي للاختصاصات الطبية

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Abstract

ABSTRUCT:BACKGROUND:CD4+CD25+ regulatory T cells are known to suppress the immune response in general, these cellswere studied in the presence of streptococcal M protein which has an important role in thepathogenesis of rheumatic heart disease.OBJECTIVE:The purpose of this study was to determine the role of streptococcal M protein in naturallyoccurring CD4+CD25+ regulatory T cells (nTregs) function and development in rheumatic heartdisease Iraqi patients.METHODS:Streptococcus pyogenes was isolated for subsequent M protein extraction. Also, peripheral bloodnTregs and CD4+ T cells were isolated by using Magnetic Cell Separation System (MACS). Tissueculture system for isolated cells was performed in the presence and absence of M proteinstimulation. Cell count was performed, also, TNF-α, and IL-4 were determined in culturesupernatant using ELISA system.RESULTS:It was found a highly significant positive association between the number of the cellularproliferation for both nTregs and CD4+ T cells with or without streptococcal M protein stimulationin isolated cell culture systems (p < 0.01), but, there found a highly significant negative correlationbetween the mean number of nTregs and CD4+ T cells in mixed culture system in the absence ofM protein (r = -0.995). whereas, in the presence of M protein, there was a positive non-significantassociation between the mean number of both nTregs and CD4+ T cells (r = 0.353) (p > 0.05).Results obtained from ELISA test revealed that M protein-stimulated CD4+ T cells produced IL-4in very little amounts (< 4 pg/ml) in all cultures of samples and there was no significant differenceamong them. Whereas, TNF-α was produced in higher concentrations in the culture supernatantswhen compared with IL-4.CONCLUSION:Streptococcal M protein has an important role in increasing the proliferation of both CD4+CD25+regulatory T cells and CD4+ T cells, but the newer generation of CD4+CD25+ regulatory T cells inthe presence of M protein has lower suppressive activity against CD4+ T cells.


Article
Anti-inflammatory Role of IL-4 in Patients with Rheumatic Mitral Valve Stenosis

Authors: Zaman I. L. Al-Kaabi --- Nidhal Abdul-Muhaimen
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2010 Volume: 52 Issue: 3 Pages: 309-311
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: IL-4 is an antibodies inflammatory cytokine which has an important role in protecting against the inflammatory reactions in most of diseases. Here, we try to highlights the role of this cytokine in chronic Rheumatic heart disease and its correlation with the extent of histopathological abnormalities.Patients and Methods: Rheumatic mitral valve surgical fragments were taken from a total of 48 Iraqi patients with chronic rheumatic heart disease under mitral valve replacement surgery in Ibn Al-Bitar Hospital for Cardiac Surgery-Iraq-Baghdad. Paraffin embedded mitral valve tissue sections were prepared. IL-4-expressing cells were detected by using immunohistochemical staining technique and histopathological picture was studied by using hematoxylin and eosin staining.
Results: There were lower numbers of IL-4 positive cells in all patients under study in general, but very lower IL-4 positive cells percentage was recorded in high risk group patients. There was no significant difference in the distribution of IL-4 mean positive cell’s count among all patients (p > 0.05). There was a correlation of IL-4 with the extent of histopathological abnormalities, and odds ratio results displayed that the histopathological abnormalities which recorded in the case group 4 times than that occurred in the control group.Conclusion: IL-4 plays an important role in regulating the inflammatory responses against the heart in chronic rheumatic heart disease


Article
CIRCULATING-PERIPHERAL BLOOD NATURALLY OCCURRING CD4+CD25+ REGULATORY T CELLS AND CD4+ T CELLS IN CHRONIC RHEUMATIC HEART DISEASE

Authors: Zaman I.L. Al-Kaabi زمن ابراهيم الكعبي --- Nidhal A.M. Mohammed نضال عبد المهيمن محمد
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2011 Volume: 9 Issue: 1 Pages: 24-33
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background: The development of autoimmune disease involves a breakdown in the mechanisms that control T cell tolerance to self antigens, these mechanisms are many and complex, and they integrate as immunoregulation. Among the cells that might be responsible for this regulation is a specific type of T cells which has the ability to downregulate the differentiation of helper cells or antigen specific effector cells. The main subset of these suppressor T cells is the naturally occurring CD4+CD25+ regulatory T cells (n Tregs) which are the most important and they derived as a functionally mature population from the thymus.Objective: The purpose of this study was to determine the correlation between the numbers of circulating CD4+CD25+ regulatory T cells (nTregs) and CD4+ T cells in chronic rheumatic heart disease patients.Methods: Peripheral blood samples were taken from 48 Iraqi patients with chronic rheumatic heart disease (CRHD). Lymphocytes were isolated from the peripheral blood, nTregs and CD4+ T cells; also, cell numbers were detected by using immunofluorescence technique.Results: In general, nTregs were found in lower numbers in the peripheral blood of CRHD patients in different study groups than in healthy control group, whereas, CD4+ T cells were found in higher numbers in some of patients than controls. Also, our results revealed that there was a significant negative correlation between naturally occurring CD4+CD25+ regulatory T cells and CD4+ T cells in all study groups.Conclusions: Our finding confirmed that there is a significant correlation between circulating nTregs and CD4+ T cells in chronic rheumatic heart disease.Key words: CD4+CD25+ regulatory T cells, CD4+ T cells, chronic rheumatic heart disease.


Article
FOXP3-INFILTRATING CELLULAR EXPRESSION IN RHEUMATIC MITRAL VALVE TISSUE LESIONS

Authors: Zaman I.L. Al-Kaabi زمن ابراهيم الكعبي --- Nidhal A.M. Mohammed نضال عبد المهيمن محمد
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2011 Volume: 9 Issue: 2 Pages: 102-107
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background: The Foxp3 gene is exclusive. It found in nTregs and correlates with the suppressive activity of these cells.Objective: To detect Foxp3 expression in infiltrating cells in the rheumatic mitral valve tissue lesions and its correlation with the extent of histopathological abnormalities when considered naturally occurring CD4+CD25+ regulatory T cells (nTregs) as the main expressers for this protein.Methods: Rheumatic mitral valve surgical fragments were taken from a total of 48 Iraqi patients with chronic rheumatic heart disease underwent mitral valve replacement in Ibn Al-Bitar Hospital for Cardiac Surgery-Baghdad-Iraq from October 2006-September 2007. Formalin-fixed paraffin-embedded mitral valve tissue sections were prepared. Foxp3-expressing cells were detected by using immunohistochemical staining technique, and histopathological picture was visualized by using hematoxylin and eosin staining.Results: Our results showed that there were no significant association between Foxp3 expression and the history of acute rheumatic fever (negative or positive), and/or the frequency of attacks (single or multiple) among all groups under study (p > 0.05). Also, we found a significant negative correlation between the percentage of Foxp3 strong positive cells and the extent of histopathological abnormalities.Conclusions: There was a negative correlation between Foxp3 strong positive expression and the extent of histopathological abnormalities which reinforce the immunosuppressive role of nTregs against the inflammatory and autoimmune reactions in chronic rheumatic heart disease. Key words: Foxp3, CD4+CD25+ regulatory T cells, mitral valve

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