%0 Journal Article %A Lühder, Fred %A Höglund, Petter %A Allison, James P. %A Benoist, Christophe %A Mathis, Diane %T Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Regulates the Unfolding of Autoimmune Diabetes %D 1998 %R 10.1084/jem.187.3.427 %J The Journal of Experimental Medicine %P 427-432 %V 187 %N 3 %X Evidence has been accumulating that shows that insulin-dependent diabetes is subject to immunoregulation. To determine whether cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is involved, we injected anti–CTLA-4 mAb into a TCR transgenic model of diabetes at different stages of disease. When injected into young mice, months before they would normally become diabetic, anti–CTLA-4 induced diabetes rapidly and essentially universally; this was not the result of a global activation of T lymphocytes, but did reflect a much more aggressive T cell infiltrate in the pancreatic islets. These effects were only observed if anti–CTLA-4 was injected during a narrow time window, before the initiation of insulitis. Thus, engagement of CTLA-4 at the time when potentially diabetogenic T cells are first activated is a pivotal event; if engagement is permitted, invasion of the islets occurs, but remains quite innocuous for months, if not, insulitis is much more aggressive, and diabetes quickly ensues. %U http://jem.rupress.org/content/jem/187/3/427.full.pdf