| Title | Neonatal β-Cell Apoptosis: A Trigger for Autoimmune Diabetes? | |
| Author | : | Jacqueline D. Trudeau, Jan P. Dutz, Edith Arany, David J. Hill, Warren E. Fieldus, and Diane T. Finegood |
| Jurnal | : | DIABETES, VOL. 49, JANUARY 2000 |
ABSTRACT
In neonatal rodents, the -cell mass undergoes a phase of remodeling that includes a wave of apoptosis. Using both mathematical modeling and histochemical detection methods, we have demonstrated that β-cell apoptosis is significantly increased in neonates as compared with adult rats, peaking at ~2 weeks of age.
Other tissues, including the kidney and nervous system, also exhibit neonatal waves of apoptosis, suggesting that this is a normal developmental phenomenon.
We have demonstrated that increased neonatal β-cell apoptosis is also present in animal models of autoimmune diabetes, including both the BB rat and NOD mouse.
Traditionally, apoptosis has been considered a process that does not induce an immune response. However, recent studies indicate that apoptotic cells can do the following: 1) display autoreactive antigen in their surface blebs; 2) preferentially activate dendritic cells capable of priming tissue-specific cytotoxic T-cells; and 3) induce the formation of autoantibodies.
These findings suggest that in some circumstances physiological apoptosis may, in fact, initiate autoimmunity. Initiation of β-cell–directed autoimmunity in murine models appears to be fixed at ~15 days of age, even when diabetes onset is dramatically accelerated.
Taken together, these observations have led us to hypothesize that the neonatal wave of β-cell apoptosis is a trigger for -cell–directed autoimmunity.
Diabetes 4 9 :1–7, 2000
About the Author:
Jacqueline D. Trudeau, MD, PhD, is a resident at the Department of Anesthesia, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
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