T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes
Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet tr...
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doaj-c22e5c1788524e34916c9959360c68962020-11-25T00:24:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922017-12-01810.3389/fendo.2017.00343317011T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 DiabetesAdam L. Burrack0Tijana Martinov1Brian T. Fife2Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United StatesDepartment of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United StatesDepartment of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United StatesType 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications. Ideally a successful approach would target only the destructive immune cells and leave the remaining immune system intact to fight foreign pathogens. This review discusses the autoimmune diabetes disease process, diabetic complications that warrant a transplant, and alloimmunity. First, we describe the current understanding of autoimmune destruction of beta cells including the roles of CD4 and CD8 T cells and several possibilities for antigen-specific tolerance induction. Second, we outline diabetic complications necessitating beta cell replacement. Third, we discuss transplant recognition, potential sources for beta cell replacement, and tolerance-promoting therapies under development. We hypothesize that a better understanding of autoreactive T cell targets during disease pathogenesis and alloimmunity following transplant destruction could enhance attempts to re-establish tolerance to beta cells.http://journal.frontiersin.org/article/10.3389/fendo.2017.00343/fulltype 1 diabetesimmunologyautoimmune diseasestransplantation immunologytolerance inductionT cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adam L. Burrack Tijana Martinov Brian T. Fife |
spellingShingle |
Adam L. Burrack Tijana Martinov Brian T. Fife T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes Frontiers in Endocrinology type 1 diabetes immunology autoimmune diseases transplantation immunology tolerance induction T cells |
author_facet |
Adam L. Burrack Tijana Martinov Brian T. Fife |
author_sort |
Adam L. Burrack |
title |
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes |
title_short |
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes |
title_full |
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes |
title_fullStr |
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes |
title_full_unstemmed |
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes |
title_sort |
t cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2017-12-01 |
description |
Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications. Ideally a successful approach would target only the destructive immune cells and leave the remaining immune system intact to fight foreign pathogens. This review discusses the autoimmune diabetes disease process, diabetic complications that warrant a transplant, and alloimmunity. First, we describe the current understanding of autoimmune destruction of beta cells including the roles of CD4 and CD8 T cells and several possibilities for antigen-specific tolerance induction. Second, we outline diabetic complications necessitating beta cell replacement. Third, we discuss transplant recognition, potential sources for beta cell replacement, and tolerance-promoting therapies under development. We hypothesize that a better understanding of autoreactive T cell targets during disease pathogenesis and alloimmunity following transplant destruction could enhance attempts to re-establish tolerance to beta cells. |
topic |
type 1 diabetes immunology autoimmune diseases transplantation immunology tolerance induction T cells |
url |
http://journal.frontiersin.org/article/10.3389/fendo.2017.00343/full |
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