| Περίληψη: | 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.
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