T regulatory subpopulation characterization in multiple sclerosis patients and analysis of their function

• Κύριος συγγραφέας: Πάππου, Ευθυμία
• Άλλοι συγγραφείς: Μουζάκη, Αθανασία
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2019
• Θέματα: T regulatory lymphocytes; Multiple sclerosis; Τ ρυθμιστικά λεμφοκύτταρα; Σκλήρυνση κατά πλάκας; 616.834

Regulatory populations, CD4+CD25+FoxP3+, CD4+CD25+CD127low/-, CD3+CD4+HLA-G+, CD3+CD8+HLA-G+, CD3+CD8+CD28- ,CD3+CD56+ (NKTs) and CD3-CD56bright (NKs) are responsible for antigen recognition and immune system’s regulation. They are critical for autoimmune diseases such as multiple sclerosis (MS). Myelin oligodendrocyte protein (MOG) is a protein of the myelin sheath and MOG peptides act as antigens in patients with MS. The purpose of this study was to evaluate the changes of regulatory subsets and other cell populations in healthy individuals (HC) and patients ± wild type MOG35-55 analogue. Materials and Methods: Heparinized peripheral blood was drawn from nine healthy donors (HC) - (4F/5M, range 23-41 y.o) and eleven patients (8F/3M, range 36-58 y.o) with RR-MS. Peripheral blood mononuclear cells were isolated and 106cells/mL were cultured± MOG35-55 (10pg/ml) for 72h. T cell populations (CD3+, CD4+, CD8+, CD25+, CD28+), Treg subsets (CD4+CD25+/hiCD127low/-, CD4+CD25+/hiFoxP3+, CD3+CD4+HLA-G+, CD3+CD8+HLA-G+ CD3+CD8+CD28-), NKTs (CD3+CD56+), NKs (CD3-CD56hi) and T effector (CD4+CD25-) cells were determined by flow cytometry. Results: The CD4+CD25+/hiFoxP3+ cells were at higher levels in the HC group without MOG35-55, compared to R-MS group, but in AcP patients’ samples +MOG35-55 we observed the highest effect. CD4+CD25+/hiCD127low/- cells were significantly reduced in RR-MS compared to the HC samples, whereas the peptide presence caused a minor increase in HC and AcP groups, but a trend to peptide response characterized the R-MS group. CD3+CD56+ and CD3+CD8+CD28- populations appeared decreased in RR-MS groups compared to HC differing statistically significantly in the latter, but weren’t affected by the presence of peptide in any group. A different expression pattern was observed in CD3-CD56hi cells without the peptide which were reduced in AcP group but increased in the R-MS compared to physiological samples. No difference was observed when the peptide was present. The populations that were increased in RR-MS patients were CD3+CD4+HLA-G+ and CD3+CD8+HLA-G+ withthe former exhibiting statistically significant differences when compared to HC donors. Interestingly, MOG35-55 presence caused a statistically significant decrease in HC group when CD3+CD8+HLA-G+ population was studied, whereas no difference or a minor decrease was observed in AcP and R-MS groups respectively. Finally, in CD3+CD4+HLA-G+ population, the presence of the peptide caused a decrease in HC and AcP groups but the opposite was noticed regarding R-MS group. Conclusions: MOG35-55 presence didn’t affect any of the T populations apart from the CD4+CD25+ effector population of the R-MS group confirming the expected response. On the other hand there was no statistically significant effect of peptide in the populations with regulatory properties possibly due to lack of samples or functionality impairment. Although, the low number of subjects in AcP group does not allow us to address whether MOG35-55 actually affects CD4+CD25+/hiFoxP3+ cells, its impact on their frequency triggers us to further investigate it.