Control of type 1 diabetes by CD4 + Foxp3 + regulatory T cells: lessons from mouse models and implications for human disease

In recent years, there has been a revival of the concept of CD4 + regulatory T (T reg ) cells as being a central control point in various immune responses, including autoimmune responses and immunity to transplants, allergens, tumours and infectious microbes. The current literature suggests that T reg cells are diverse in their phenotype and mechanism(s) of action, and as such, may constitute a myriad of naturally occurring and induced T cell precursors with variable degrees of regulatory potential. In this review, we summarize research from various laboratories, including our own, showing that CD4 + Foxp3 + T reg cells are critical in the control of type 1 diabetes (T1D) in mouse models and humans. In this review, we also discuss cellular and molecular determinants that impact CD4 + Foxp3 + T reg cell development and function and consequential resistance to organ‐specific autoimmune disease. Recent advances in the use of CD4 + Foxp3 + T reg cellular therapy to promote immunological tolerance in the absence of long‐term generalized immunosuppression are also presented. Copyright © 2009 John Wiley & Sons, Ltd.