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1.  TLR agonists abrogate costimulation blockade-induced mixed chimerism and transplantation tolerance 
We investigated the mechanisms by which toll-like receptor (TLR) agonists affect the induction of mixed chimerism and skin allograft survival in mice treated with costimulation blockade (CB). We report that TLR agonists prevent the generation of mixed chimerism by breaking tolerance in the alloreactive CD4+ and CD8+ T cell compartments, and that type I interferon (IFN) is important in this process. Understanding how environmental perturbations affect CB-induced transplantation tolerance may lead to more effective regimens that can be used as an approach for the treatment of type 1 diabetes, for which the transplantation of pancreatic islets is a promising therapy.
doi:10.1196/annals.1447.034
PMCID: PMC2626129  PMID: 19120285
costimulation blockade; Toll-like receptors; hematopoietic chimerism; tolerance
2.  The Circle between the Bedside and the Bench: Toll-Like Receptors in Models of Viral Induced Diabetes 
Animal models provide many strategies to unravel the complex interplay of genetic, immunological, and environmental factors involved in the pathogenesis of type 1A (autoimmune) diabetes. Diabetes can be studied at multiple levels and new technological advancements provide insights into the functioning of organelle and cellular structures. The role of innate immunity in the response to environmental pathogens has provided possible biochemical and molecular mechanisms which can explain certain clinical diabetes events. These investigations may uncover new therapies and strategies to prevent type 1A diabetes.
doi:10.1196/annals.1447.025
PMCID: PMC2625298  PMID: 19120279
Toll-Like Receptors; Viruses; Type 1A diabetes
3.  Humanized Mice for the Study of Type 1 Diabetes and Beta Cell Function 
Our understanding of the basic biology of diabetes has been guided by observations made using animal models, particularly rodents. However, humans are not mice, and outcomes predicted by murine studies are not always representative of actual outcomes in the clinic. In particular, investigators studying diabetes have relied heavily on mouse and rat models of autoimmune type 1-like diabetes, and experimental results using these models have not been representative of many of the clinical trials in type 1 diabetes. In this manuscript, we describe the availability of new models of humanized mice for the study of three areas of diabetes. These include the use of humanized mice for the study of 1) human islet stem and progenitor cells, 2) human islet allograft rejection, and 3) human immunity and autoimmunity. These humanized mouse models provide an important pre-clinical bridge between in vitro studies and rodent models and the translation of discoveries in these model systems to the clinic.
doi:10.1196/annals.1447.009
PMCID: PMC2620029  PMID: 19120266
Humanized mouse; Diabetes; Beta cell function

Results 1-3 (3)