|
|
Immunogenicity of induced pluripotent stem cells (iPSC)
Tejklová, Tereza ; Drbal, Karel (advisor) ; Hájková, Michaela (referee)
Ectopic expression of several transcription factors into the somatic cells allows us to artificially dedifferentiate them into induced pluripotent stem cells (iPSC), which show great promise in regenerative medicine and personalized disease modelling, as well as diagnostic tools. Unique attribute of iPSC is the possibility of creating autologous cells for each patient, which could be used for transplantation without fear of immune rejection. However, cells differentiated from iPSC generally display decreased expression of MHC I glycoproteins, which leads to the activation of NK cells of innate immunity. T cells, the part of adaptive immunity, are activated after recognition of antigen peptide or foreign MHC I glycoproteins only in co-operation with costimulatory molecules, which are not usually expressed on iPSC. During dedifferentiation, cells keep the epigenetic profile of the source cell, which can result in the abnormal expression of genes within derived cell lines. Overall immunogenicity depends on the method of iPSC preparation, with respect to genomic stability. Another important factor is the immune environment of transplantation site as well as the tissue damage caused during transplantation. This results in the presentation of danger signals (DAMPs), which are then recognized by pattern...
|
|
|
Effect of gluten-free diet on immune cell subsets in the NOD mouse model of type 1 diabetes
Tejklová, Tereza ; Funda, David (advisor) ; Krulová, Magdaléna (referee)
Type 1 diabetes (T1D) is an autoimmune disease leading to destruction of insulin-secreting pancreatic -cells. Environmental factors e.g. exposures to infections, dietary components play a substantial role in etiopathogenesis of T1D and are responsible for rapid increase of T1D incidence in past decades, preferentially in developed countries. Despite long record of T1D research no causative cure or efficient prevention exists. While gluten displays proinflammatory properties, gluten-free diet (GFD) has been documented by several studies as a strong diabetes- preventive environmental factor in spontaneous animal models of T1D, mostly in NOD mouse. The aim of this thesis is to better characterize effects of GFD on the immune system of NOD mouse. Using flow cytometry, we compared effects of GFD vs standard (STD) Altromin diets on NK cell subsets, Tregs, as well as other regulatory cell subsets and their cytokine profile in prediabetic SPF NOD females that were exposed to the diets since "in utero". A reference diabetes incidence in NOD females in our SPF facility kept on STD and GFD was recorded. Diabetes-preventive capacity of GFD were tested by using the NOD-SCID model of diabetes transfer, in which splenocytes from at-onset NOD females kept on GFD or STD were transferred to NOD-SCID recipients....
|
|
|
Immunogenicity of induced pluripotent stem cells (iPSC)
Tejklová, Tereza ; Drbal, Karel (advisor) ; Hájková, Michaela (referee)
Ectopic expression of several transcription factors into the somatic cells allows us to artificially dedifferentiate them into induced pluripotent stem cells (iPSC), which show great promise in regenerative medicine and personalized disease modelling, as well as diagnostic tools. Unique attribute of iPSC is the possibility of creating autologous cells for each patient, which could be used for transplantation without fear of immune rejection. However, cells differentiated from iPSC generally display decreased expression of MHC I glycoproteins, which leads to the activation of NK cells of innate immunity. T cells, the part of adaptive immunity, are activated after recognition of antigen peptide or foreign MHC I glycoproteins only in co-operation with costimulatory molecules, which are not usually expressed on iPSC. During dedifferentiation, cells keep the epigenetic profile of the source cell, which can result in the abnormal expression of genes within derived cell lines. Overall immunogenicity depends on the method of iPSC preparation, with respect to genomic stability. Another important factor is the immune environment of transplantation site as well as the tissue damage caused during transplantation. This results in the presentation of danger signals (DAMPs), which are then recognized by pattern...
|
guest ::
