Targeting Regulatory T Cells in the Treatment of Type 1 Diabetes Mellitus

S.M.      Cabrera; M.R.      Rigby; R.G.      Mirmira

Abstract

Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease resulting in islet β cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. T1DM has classically been attributed to the pathogenic actions of auto-reactive effector T cells(Teffs) on the β cell. Recent literature now suggests that a failure of a second T cell subtype, known as regulatory T cells (Tregs), plays a critical role in the development of T1DM. During immune homeostasis, Tregs counterbalance the actions of autoreactive Teff cells, thereby participating in peripheral tolerance. An imbalance in the activity between Teff and Tregs may be crucial in the breakdown of peripheral tolerance, leading to the development of T1DM. In this review, we summarize our current understanding of Treg function in health and in T1DM, and examine the effect of experimental therapies for T1DM on Treg cell number and function in both mice and humans.

Keywords: Autoimmunity, effector T cells, regulatory T cells, Teffs, Tregs, Type 1 diabetes mellitus, autoimmune disease, hyperglycemic, phenotype, antigens, autoantigens, viral infection, cytokines, insulitis, chemokines