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Effect of diabetogenic autoantigens on the cytokine production of peripheral blood mononuclear cells from type 1 diabetic patients
Labiková, Jana ; Štechová, Kateřina (advisor) ; Holáň, Vladimír (referee)
5 Abstract Type 1 diabetes (T1D) is a serious organ-specific autoimmune disease characterised by irreversible destruction of pancreatic β-cells by immune system. This process results in an absolute insulin deficiency. Both genetical predisposition and environmental factors influence the development of the disease. β-cell destruction is mediated by cellular components of an immune system. Proinflammatory Th1 response is considered as most pathological. Autoimmune destruction of β-cells can be identified by the detection of specific serum autoantibodies a long time before the T1D clinical onset. Currently, there is no efficient cure available to prevent or at least to delay the destructive insulitis. This diploma thesis describes the influence of synthetic diabetogenic autoantigens GAD65 and IA2 on the cytokine response of peripheral blood mononuclear cells (PBMC) obtained from T1D patients with regards to their antibody profile. The study has been carried out on patients with confirmed T1D diagnosis who tested positive for anti-GAD65 and/or anti-IA2 autoantibodies. By using flow cytometry we measured the cell type ratio in PBMC samples. The cells have been stimulated by three different concentrations of antigens and their IFNγ and IL-17 production has been detected by ELISPOT assay. In the case of both...
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Th17 lymphocytes and autoimmunity diseases with the intention of diabetes 1. type
Labiková, Jana ; Štechová, Kateřina (advisor) ; Procházková, Jana (referee)
Th17 cells were recently identified as a cell source of IL-17. They turned up to be a T cell lineage independent of previously described Th1 and Th2. The differentiation of naive CD4+ T cells towards Th17 requires the combination of TGFβ (a cytokine essential for the development of anti-inflammatory regulatory T cells) plus IL-6 or IL-21. IL-23 is required for in vivo function and phenotype maintenance of Th17. STAT3 and RORγt were identified as pivotal transcription factors in Th17 differentiation program. Th17 proved to have pro- inflammatory effects and are characterized by the production of IL-17A, IL-17F and IL-22 - cytokines implicated in host defense against certain extracellular pathogens. The cytokine products of Th17 cells act on wide range of cell types. They induce cytokines, chemokines and metalloproteinases and they also mediate neutrophil recruitment and production of antimicrobial peptides. Autoreactive Th17 are highly pathogenic and the production of IL-17 has been detected in several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, Crohn's disease and type 1 diabetes. These diseases were thought to be mediated by Th1 cells, but it is becoming increasingly clear that the regulation of autoimmunity is influenced at least in some diseases by Th17 cells as well.
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Effect of diabetogenic autoantigens on the cytokine production of peripheral blood mononuclear cells from type 1 diabetic patients
Labiková, Jana ; Štechová, Kateřina (advisor) ; Holáň, Vladimír (referee)
5 Abstract Type 1 diabetes (T1D) is a serious organ-specific autoimmune disease characterised by irreversible destruction of pancreatic β-cells by immune system. This process results in an absolute insulin deficiency. Both genetical predisposition and environmental factors influence the development of the disease. β-cell destruction is mediated by cellular components of an immune system. Proinflammatory Th1 response is considered as most pathological. Autoimmune destruction of β-cells can be identified by the detection of specific serum autoantibodies a long time before the T1D clinical onset. Currently, there is no efficient cure available to prevent or at least to delay the destructive insulitis. This diploma thesis describes the influence of synthetic diabetogenic autoantigens GAD65 and IA2 on the cytokine response of peripheral blood mononuclear cells (PBMC) obtained from T1D patients with regards to their antibody profile. The study has been carried out on patients with confirmed T1D diagnosis who tested positive for anti-GAD65 and/or anti-IA2 autoantibodies. By using flow cytometry we measured the cell type ratio in PBMC samples. The cells have been stimulated by three different concentrations of antigens and their IFNγ and IL-17 production has been detected by ELISPOT assay. In the case of both...
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Th17 lymphocytes and autoimmunity diseases with the intention of diabetes 1. type
Labiková, Jana ; Procházková, Jana (referee) ; Štechová, Kateřina (advisor)
Th17 cells were recently identified as a cell source of IL-17. They turned up to be a T cell lineage independent of previously described Th1 and Th2. The differentiation of naive CD4+ T cells towards Th17 requires the combination of TGFβ (a cytokine essential for the development of anti-inflammatory regulatory T cells) plus IL-6 or IL-21. IL-23 is required for in vivo function and phenotype maintenance of Th17. STAT3 and RORγt were identified as pivotal transcription factors in Th17 differentiation program. Th17 proved to have pro- inflammatory effects and are characterized by the production of IL-17A, IL-17F and IL-22 - cytokines implicated in host defense against certain extracellular pathogens. The cytokine products of Th17 cells act on wide range of cell types. They induce cytokines, chemokines and metalloproteinases and they also mediate neutrophil recruitment and production of antimicrobial peptides. Autoreactive Th17 are highly pathogenic and the production of IL-17 has been detected in several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, Crohn's disease and type 1 diabetes. These diseases were thought to be mediated by Th1 cells, but it is becoming increasingly clear that the regulation of autoimmunity is influenced at least in some diseases by Th17 cells as well.
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