Επαγωγή της έκφρασης του μορίου HLA- G in vitro σε λεμφοκύτταρα περιφερικού αίματος υγιών ατόμων και λειτουργικός χαρακτηρισμός αυτών

• Κύριος συγγραφέας: Ζούδιαρη, Αναστασία
• Άλλοι συγγραφείς: Σπυριδωνίδης, Αλέξανδρος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2013
• Θέματα: Lymphocytes; HLA-G; Graft-versus-host disease (GVHD); Λεμφοκύτταρα; 617.441 059 2

There is an urgent need for novel preventive and therapeutic strategies for graft versus host disease (GvHD) occurring after allogeneic hematopoietic cell transplantation (allo-HCT). T-cell-based immunotherapies have been developed, however there are still some hurdles for the use of currently availably regulatory T-cells in clinical practice (naturally occurring FOXP3 + nTregs and inducible regulatory T cells), mainly owing to the lack of specific cell surface markers. The hypomethylating agent azacytidine (5-aza-dC) has been shown to generate immunoregulatory T-cells ex vivo. Interestingly, it has been shown that genes other than FOXP3 are responsible for the suppressor function of 5-aza-dC induced T-regs. HLA-G is a surface molecule with potent immunoregulatory functions which is normally expressed during pregnancy protecting the “semi-allogeneic” fetus from maternal immune attack and then is epigenetically repressed. The aim of this study was the induction of HLA-G expression in T-lymphocytes with the use of the demethylating agent 5-Aza-dC and investigation of their possible immunoregulatory properties. Our results showed that short in vitro treatment of peripheral blood T-cells with 5-aza-dC induces HLA-G expression and, more importantly, these induced HLA-G + T-cells could suppress lymphoproliferation when added as third party cells in mixed lymphocyte cultures. This suppression seems to be reduced after HLA-G neutralization and cell-to-cell contact independent. Furthermore, these induced HLA-G + T-cells show a reduced proliferation to allogeneic stimuli. Taken together, our results indicate the ex vivo production of HLA-Gpos T-lymphocytes with immunoregulatory properties. Our long term goal is the use of this population as adoptive cellular therapy for GvHD and other T-cell mediated diseases.