Treg in type 1 diabetes.
At the time of this writing, a major void exists; the lack of a method to prevent and/or reverse type 1 diabetes in humans. We believe this void to a large extent is the result of our lack in understanding the mechanisms of autoimmunity that underlie beta cell destruction, a failure to understand the immunologic factors that contribute to type 1 diabetes, and the absence of immunologic tools which would allow for a better understanding of the mechanisms underlying disease development and monitoring of therapeutic interventions. Due to this, an intense degree of research interest has recently been generated to understand the mechanisms that regulate the immune response and form a state of immunological tolerance. While some progress has been made towards these goals, additional investigations are needed to address the aforementioned knowledge voids including the role for regulatory T cells (Treg), defined by their co-expression of CD4 and CD25 as well as the transcription factor FOXP3, in the pathogenesis and natural history of type 1 diabetes. We and others have recently reported findings related to the frequency and function of Treg cells in type 1 diabetes, yet the resulting literature represents a somewhat conflicting body of findings. Our studies did not support the notion that altered Treg frequencies are associated with type 1 diabetes, but rather did identify alterations in the functional (i.e., suppressive) activities of these cells in subjects with the disease. The need to bring resolution to the aforementioned published discrepancies in frequency and function of Treg in type 1 diabetes represents the impetus for this critical review. In addition, we hope to highlight the need for expanded studies that address specific knowledge gaps regarding the cellular and molecular mechanism(s) related to the frequency and function of Treg.
Brusko
Todd
T
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Atkinson
Mark
M
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse