Re-establishing immune tolerance in type 1 diabetes via regulatory T cells.

Type 1 diabetes (T1D) is a disease in which tolerance to self-antigens, such as insulin, is broken leading to expansion of autoreactive T cells that attack pancreatic beta cells with consequent loss of insulin production. Regulatory T cells (Tregs) represent a specific T cell subset that plays a key role in inducing and maintaining immunological tolerance to self and non-self antigens. The naturally occurring CD4+CD25+ Tregs (nTregs) originate from the thymus, constitutively express the transcription factor FOXP3, and suppress immune responses mainly via cell-cell contact. Depletion of nTregs results in systemic autoimmune diseases in mice and, vice versa, transfer of nTregs prevents development of autoimmune diseases. Regulatory T type 1 (Tr1) cells are inducible Tregs generated in the periphery by chronic exposure to antigens in the presence of interleukin (IL)10. Tr1 cells are defined by their unique cytokine production profile (i.e. IL10++, IL5+, TGFbeta+, IL4-, IL2(low), IFNgamma(low). Tr1 cells are induced by a specialized subset of tolerogenic dendritic cells and suppress undesired immune responses mainly through production of IL10 and TGFbeta. Interestingly,Trl cells modulate responses to self-antigens such as insulin- and islet-derived peptides. In vitro expansion/induction of Tregs can be therefore envisaged as a therapeutic tool for re-establishing self-tolerance in T1D subjects.