Replenishing Peripheral CD4+ Regulatory T Cells: A Possible Immune-Intervention Strategy in Type 1 Diabetes?

Controlling the diabetogenic activity of peripheral islet antigen-specific T cells is essential to halt the progression of autoimmunity that leads to the development of type 1 diabetes mellitus (T1DM). Over the past years, evidence has been gathered to suggest that the dysfunction of CD4(+)CD25(+) regulatory T (Treg) cells, and the interleukin-10 (IL10) -secreting type 1 regulatory T (Tr1) cells are associated with disease onset in diabetic patients. Although CD4(+)CD25(+) Treg cells develop as a distinct lineage of T cells in the thymus, results from recent studies have shown that they can also arise independently from the peripheral pool of conventional CD4(+) lymphocytes. These observations have led to the development of various methods to convert peripheral CD4(+) T cells into CD4(+)CD25(+) Treg and Tr1 cells in vitro or to induce the development and expansion of Treg cell subsets in vivo. This article reviews the progress made in Treg cell recruitment in vivo that involves the potential for the prevention or even reversal of T1DM.