Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes
Type 1 diabetes, the immune mediated form of diabetes, represents a prototypical organ specific autoimmune disease in that insulin producing pancreatic islets are specifically targeted by T cells. The disease is now predictable in humans with the measurement of type 1 diabetes associated autoantibod...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00365/full |
| _version_ | 1811204200803074048 |
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| author | Maki Nakayama Aaron W. Michels |
| author_facet | Maki Nakayama Aaron W. Michels |
| author_sort | Maki Nakayama |
| collection | DOAJ |
| description | Type 1 diabetes, the immune mediated form of diabetes, represents a prototypical organ specific autoimmune disease in that insulin producing pancreatic islets are specifically targeted by T cells. The disease is now predictable in humans with the measurement of type 1 diabetes associated autoantibodies (islet autoantibodies) in the peripheral blood which are directed against insulin and beta cell proteins. With an increasing incidence of disease, especially in young children, large well-controlled clinical prevention trials using antigen specific immunotherapy have been completed but with limited clinical benefit. To improve outcomes, it is critical to understand the antigen and T cell receptor repertoires of those cells that infiltrate the target organ, pancreatic islets, in human type 1 diabetes. With international networks to identify organ donors with type 1 diabetes, improved immunosequencing platforms, and the ability to reconstitute T cell receptors of interest into immortalized cell lines allows antigen discovery efforts for rare tissue specific T cells. Here we review the disease pathogenesis of type 1 diabetes with a focus on human islet infiltrating T cell antigen discovery efforts, which provides necessary knowledge to define biomarkers of disease activity and improve antigen specific immunotherapy approaches for disease prevention. |
| first_indexed | 2024-04-12T03:07:15Z |
| format | Article |
| id | doaj.art-888735439b2b4e04b922ece601a29695 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T03:07:15Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-888735439b2b4e04b922ece601a296952022-12-22T03:50:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00365425018Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 DiabetesMaki NakayamaAaron W. MichelsType 1 diabetes, the immune mediated form of diabetes, represents a prototypical organ specific autoimmune disease in that insulin producing pancreatic islets are specifically targeted by T cells. The disease is now predictable in humans with the measurement of type 1 diabetes associated autoantibodies (islet autoantibodies) in the peripheral blood which are directed against insulin and beta cell proteins. With an increasing incidence of disease, especially in young children, large well-controlled clinical prevention trials using antigen specific immunotherapy have been completed but with limited clinical benefit. To improve outcomes, it is critical to understand the antigen and T cell receptor repertoires of those cells that infiltrate the target organ, pancreatic islets, in human type 1 diabetes. With international networks to identify organ donors with type 1 diabetes, improved immunosequencing platforms, and the ability to reconstitute T cell receptors of interest into immortalized cell lines allows antigen discovery efforts for rare tissue specific T cells. Here we review the disease pathogenesis of type 1 diabetes with a focus on human islet infiltrating T cell antigen discovery efforts, which provides necessary knowledge to define biomarkers of disease activity and improve antigen specific immunotherapy approaches for disease prevention.https://www.frontiersin.org/article/10.3389/fimmu.2019.00365/fulldiabetesautoimmunityHLAinsulinT cells |
| spellingShingle | Maki Nakayama Aaron W. Michels Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes Frontiers in Immunology diabetes autoimmunity HLA insulin T cells |
| title | Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes |
| title_full | Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes |
| title_fullStr | Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes |
| title_full_unstemmed | Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes |
| title_short | Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes |
| title_sort | determining antigen specificity of human islet infiltrating t cells in type 1 diabetes |
| topic | diabetes autoimmunity HLA insulin T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00365/full |
| work_keys_str_mv | AT makinakayama determiningantigenspecificityofhumanisletinfiltratingtcellsintype1diabetes AT aaronwmichels determiningantigenspecificityofhumanisletinfiltratingtcellsintype1diabetes |