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Hubert Kolb, Matthias von Herrath  Cell Metabolism 

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Presentation on theme: "Hubert Kolb, Matthias von Herrath  Cell Metabolism "— Presentation transcript:

1 Immunotherapy for Type 1 Diabetes: Why Do Current Protocols Not Halt the Underlying Disease Process? 
Hubert Kolb, Matthias von Herrath  Cell Metabolism  Volume 25, Issue 2, Pages (February 2017) DOI: /j.cmet Copyright © 2017 Elsevier Inc. Terms and Conditions

2 Cell Metabolism 2017 25, 233-241DOI: (10.1016/j.cmet.2016.10.009)
Copyright © 2017 Elsevier Inc. Terms and Conditions

3 Figure 1 T1D: Potential Immune versus Autoimmune Interpretation
Several key findings indicate that immune reactivity is critical to β cell loss or damage during the pathogenesis of T1D. However, none of the observations are able to prove whether an autoimmune or an immune process is responsible for β cell loss. Cell Metabolism  , DOI: ( /j.cmet ) Copyright © 2017 Elsevier Inc. Terms and Conditions

4 Figure 2 Insulitis in Human Type 1 Diabetes
Pancreatic sections were obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD). This is donor #6198, who had type 1 diabetes for 3 years. Two consecutive sections were stained for (1) glucagon, CD45, and Hoechst and (2) CD8, HLA-ABC, and Hoechst. Representative images of an islet with insulitis are shown. Left panels show CD45 in yellow, glucagon in white, and DAPI in blue. Right panels show CD8 in green, HLA-ABC in red, and DAPI in blue. Scale bars indicate 50 μm. Cell Metabolism  , DOI: ( /j.cmet ) Copyright © 2017 Elsevier Inc. Terms and Conditions

5 Figure 3 Possible Models of T1D: Early Trigger Period Model of Autoimmunity versus Chronic Immune Activation In Scenario 1, β cell-directed T cell reactivity is initiated during a trigger period early in life by unfavorable endogenous and/or exogenous factors. The immune response is carried out by memory cells of the adaptive immune response. Deletion of T cells eliminates β cell directed immunoreactivity. In Scenario 2, the chronic model innate immune and other cells of the local environment express or acquire a pro-inflammatory polarized regulatory state, which continuously re-initiates β cell-directed T cell reactivity and possibly exerts β cell toxicity independent from T cell reactivity. Deletion of T cells is followed by re-initiation of β cell-directed T cell reactivity and further progression of disease. Cell Metabolism  , DOI: ( /j.cmet ) Copyright © 2017 Elsevier Inc. Terms and Conditions


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