Regulatory T Lymphocytes (Treg): Modulation and Clinical Application

Abstract

Treg cells CD4+CD25+FOXP3+ have a specific function in the tolerance of autoantigens and regulation of the immune response. Modulation of differentiation pathways and the use of Treg cells in cell therapy have been reported in autoimmune diseases, systemic lupus erythromatosis, autoimmune hepatitis, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, bone marrow transplantation and solid organs. The expansion of Treg cells in vivo occurs through low-dose IL-2 treatment. However, because of the heterogeneity and variability of Treg cells, the isolation of peripheral blood cells, through the technique of leucopheresis by GMP (good manuring practice), for in vitro expansion is difficult, necessitating a large combination of specific and reliable cellular markers. Currently, two specific markers, Helios and neuropilin-1, are being studied to facilitate the differentiation of thymus Treg cells and peripheral Treg cells. However, Treg cells induced in vitro are unstable. Modulation of the FOXP3 gene in the CNS1 and CNS2 region is an alternative to maintaining the stability of expanded Treg cells in vitro.

Regulating the regulators: Is introduction of an antigen-specific approach in regulatory T cells the next step to treat autoimmunity?

“…These single-positive CD4 + T cells receive a TCR signal of varied strength by medullary thymic epithelial cells (mTEC) and B cells presenting the full antigen diversity of peripheral tissues. This process, facilitated through the autoimmune regulator enzyme (AIRE), which stimulates the expression of certain autologous tissue-specific proteins, drives the fate of the CD4 + T cells [33]. High-strength TCR signaling will mostly result in clonal deletion by negative selection, except for a small fraction of cells that will differentiate into Tregs.…”

“…For example, naïve Tregs are characterized by FoxP3 Lo CD45RA + CD45ROexpression, while activated "memory-like" Tregs have a Foxp3 Hi CD45RA -CD45RO + phenotype. Both subtypes express FAS receptor (CD95) and CTLA-4 [33]. Using mass cytometry and based on a range of markers associated with human Tregs (e.g.…”