Genomic analysis of the role of epigenetic methylation of promoter regions during in vitro generation of regulatory T cells induced (iTreg) from naive T cells from cord blood.

Abstract

The CD4 CD25 regulatory lymphocytes (Tregs) are recognized as the most important regulatory cells of the immune system, participating in the immune tolerance, autoimmunity, inflammation, transplantation, and participate in immune escape mechanisms in cancer and HIV infection . Tregs can be naturally occurring (nTregs), thymus-derived or induced in the periphery from naive cells (iTregs). The generation of regulatory T cells induced (iTregs) can occur from CD4 T cells in vitro by culture with antigen or polyclonal activators in the presence of immunosuppressive cytokines, or by coculture of T cells with mesenchymal stromal cells (CEM). Both types of Tregs, whether natural or induced, have similar phenotype and expression of the transcription factor forkhead box P3 (Foxp3) Tregs seem to be essential for the maintenance of immune homeostasis. But we still do not fully understand the mechanisms leading to induction of T cells in iTregs. Only, it is known that the TCR signaling pathway is an important factor in this differentiation. Our group also showed in a previous study, strong indications of the involvement of NF-kB factor in generating iTregs from coculture with CEM. Moreover, other studies show that naive CD4 T cells from cord blood can also generate iTregs by the addition of TGF-² in the presence of IL-2 in vitro. Thus, the general objective of assessing the epigenetic control, linked to the methylation status of CpG islands in promoter regions present at the genomic level, induction of regulatory T cells (iTreg) generated by in vitro activation of naive CD4 T cells (nTregs) recently isolated from umbilical cord blood and also assess the contribution of these factors in the transcriptional control of regulatory and effector lymphocytes.