Affiliation:
1. From the Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California
Abstract
We will take a journey from basic pathogenetic mechanisms elicited by viral infections that play a role in the development of type 1 diabetes to clinical interventions, where we will discuss novel combination therapies. The role of viral infections in the development of type 1 diabetes is a rather interesting topic because in experimental models viruses appear capable of both accelerating as well as decelerating the immunological processes leading to type 1 diabetes. Consequently, I will discuss some of the underlying mechanisms for each situation and consider methods to investigate the proposed dichotomy for the involvement of viruses in human type 1 diabetes. Prevention of type 1 diabetes by infection supports the so-called “hygiene hypothesis.” Interestingly, viruses invoke mechanisms that need to be exploited by novel combinatorial immune-based interventions, the first one being the elimination of autoaggressive T-cells attacking the β-cells, ultimately leading to their immediate but temporally limited amelioration. The other is the invigoration of regulatory T-cells (Tregs), which can mediate long-term tolerance to β-cell proteins in the pancreatic islets and draining lymph nodes. In combination, these two immune elements have the potential to permanently stop type 1 diabetes. It is my belief that only combination therapies will enable the permanent prevention and curing of type 1 diabetes.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference68 articles.
1. Sutherland DE, Sibley R, Xu XZ, Michael A, Srikanta AM, Taub F, Najarian J, Goetz FC: Twin-to-twin pancreas transplantation: reversal and reenactment of the pathogenesis of type I diabetes. Trans Assoc Am Physicians 97:80–87,1984
2. Eisenbarth GS: Molecular aspects of the etiology of type I diabetes mellitus. J Diabetes Complications 7:142–150,1993
3. Eisenbarth GS, Gianani R, Pugliese A, Verge CF, Pietropaolo M: Prediction and prevention of type I diabetes. Transplant Proc 26:361–362,1994
4. In't Veld P, Lievens D, De Grijse J, Ling Z, Van der Auwera B, Pipeleers-Marichal M, Gorus F, Pipeleers D: Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 56:2400–2404,2007
5. Cudworth AG: Type I diabetes mellitus. Diabetologia 14:281–291,1978
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