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Clinical and Developmental Immunology
Volume 2013, Article ID 254874, 17 pages
Review Article

Altered Immune Regulation in Type 1 Diabetes

1Second Department of Medicine, Semmelweis University, Szentkirályi Street 46, Budapest 1088, Hungary
2First Department of Obstetrics and Gynecology, Semmelweis University, Baross Street 27, Budapest 1085, Hungary

Received 16 April 2013; Revised 19 June 2013; Accepted 4 July 2013

Academic Editor: Shervin Assassi

Copyright © 2013 András Zóka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.