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 we also discuss cellular (T1D) in mouse models and humans. In this review, 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 (c) 2009 John Wiley & Sons, Ltd.