One More Piece of the Type 1 Diabetes Puzzle Solved
JAX® NOTES Issue 510, Summer 2008
Preventing diabetes is one of today's most pressing medical challenges. Thanks to Jackson Laboratory researchers Drs. David Serreze and Yi-Guang Chen, along with collaborators at Albert Einstein College of Medicine of Yeshiva University in Bronx, N.Y., and Rockefeller University in New York, N.Y., medical science is one step closer to meeting that challenge. In an exciting new development, this research team has shown that it's possible to destroy a type of rogue T cell that attacks the insulin-producing pancreatic beta cells, leading to type 1 diabetes (Mukhopadhaya et al. 2008).
Dr. Serreze and his Jackson Laboratory research group identified the rogue T cells and named them "AI4" several years ago. As is the case with other killer T cells, AI4 cells are not activated until antigen-presenting cells (APCs) "teach" them what to attack. In patients with type 1 diabetes, the APCs teach the AI4 cells to recognize the pancreatic beta cells by their cell surface antigens and attack them. Dr. Serreze's collaborators at Yeshiva and Rockefeller Universities then made an important discovery: the way an antigen is introduced to the APCs determines whether or not the AI4 cells are activated. Once this was known, the team found a way to introduce beta cell antigens in diabetes-susceptible mice in such a way as to delete the AI4 cells.
Type 1 diabetes is a complex disease, and other cell types may be involved in its pathogenesis. As Dr. Serreze ponders, "Are other kinds also implicated in diabetes, and, if so, how many of them can we kill off? The next step will be to see whether we can use this method to actually prevent diabetes in the mouse model."
(This article was adapted from a Jackson Laboratory press release.)
Reference
(Authors in bold are Jackson Laboratory scientists.)
Mukhopadhaya A, Hanafusa T, Jarchum I, Chen YG, Iwai Y, Serreze DV, Steinman RM, Tarbell KV, DiLorenzo TP. 2008. Selective delivery of beta cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice. Proc Natl Acad Sci U S A 105:6374-9.
