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Significance Regulatory T cells (Tregs) expressing the Treg-specific transcription factor Foxp3 are indispensable for suppressing hazardous immune responses such as autoimmune disease and allergy. Their stable function requires DNA hypomethylation at specific regions of Treg function-associated genes such as Foxp3. This report shows that, in the course of in vitro Treg generation from conventional T cells by antigenic stimulation in the presence of TGF-β and IL-2, deprivation of CD28 costimulatory signal can induce Treg-specific DNA hypomethylation in developing Tregs. Additional in vitro culture with IL-2 alone further stabilizes their Treg-type hypomethylation status, enabling their in vivo transfer to effectively suppress immune responses. These findings would help in producing functionally stable Tregs from disease-mediating T cells for treatment of various immunological diseases.

Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation