New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes.

Christine Bender,Sakthi Rajendran,Matthias G Von Herrath

doi:10.3389/fendo.2020.606434

Christine Bender, Sakthi Rajendran + Show 1 more

Open Access

https://doi.org/10.3389/fendo.2020.606434

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Abstract

Since the establishment of the network for pancreatic organ donors with diabetes (nPOD), we have gained unprecedented insight into the pathology of human type 1 diabetes. Many of the pre-existing “dogmas”, mostly derived from studies of animal models and sometimes limited human samples, have to be revised now. For example, we have learned that autoreactive CD8 T cells are present even in healthy individuals within the exocrine pancreas. Furthermore, their “attraction” to islets probably relies on beta-cell intrinsic events, such as the over-expression of MHC class I and resulting presentation of autoantigens such as (prepro)insulin. In addition, we are discovering other signs of beta-cell dysfunction, possibly at least in part due to stress, such as the over-expression of certain cytokines. This review summarizes the latest developments focusing on cytokines and autoreactive CD8 T cells in human type 1 diabetes pathogenesis.

Highlights

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which the pancreatic insulinsecreting beta cells are selectively destroyed
The enrichment of autoreactive CD8 T cells near the islets suggests that they become attracted to their key antigen in insulin-containing islets during disease development [15], possibly due to the upregulation of MHC class I [30] and accumulation of target autoantigen [35]
We discussed the evidence that autoreactive CD8 T cells are an integral and large part of the pancreatic leukocyte population in healthy individuals and can be detected in large numbers in donors with T1D (Figure 1)

Summary

Introduction

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which the pancreatic insulinsecreting beta cells are selectively destroyed. The fact that the autoreactive T cells are present in the pancreata of healthy donors [15] suggests a possibility of a triggering event in beta cells, which leads to the recruitment of these cells to the islets in T1D. Researchers studied T cell responses against islet and beta-cell antigens in peripheral blood to find signatures that differentiate between T1D patients and healthy individuals.

Results

Conclusion