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

• Main Authors: Christine Bender, Sakthi Rajendran, Matthias G. von Herrath
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-01-01
• Series: Frontiers in Endocrinology
• Subjects: type 1 diabetes; autoreactive CD8 T cells; human pancreas; beta cells; cytokines
• Online Access: https://www.frontiersin.org/articles/10.3389/fendo.2020.606434/full

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.