A Designer Approach To Regulating Autoimmunity In Diabetes

Success has been demonstrated with one therapeutic approach in animals that shuts down the autoreactive T cells that attack beta islet cells.. https://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4043 Type 1 diabetes is an autoimmune disorder in which the body’s own immune system attacks the beta cells of the pancreas, destroying or damaging them sufficiently to reduce or impair insulin production. Therefore, shutting down the autoreactive T cells that attack beta islet cells is one therapeutic approach that researchers have been investigating.

A molecule named cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is known to prevent T cell activation from getting out of control and as such researchers have been trying to identify ways in which to selectively engage and activate CTLA-4 to treat diabetes. In a study appearing in the August issue of the Journal of Clinical Investigation, Jeffrey Bluestone and colleagues from the University of California, San Francisco, designed and developed a transgenic mouse expressing an anti-CTLA-4 antibody on B cells that was capable of selectively inhibiting activated T cells and T cell-dependent B cell responses and prevented autoimmune diabetes in these animals. The study suggests that selective engagement of CTLA-4 in this manner represents a novel immunotherapeutic approach to the treatment of type 1 diabetes.

In an accompanying commentary, Mohamed H. Sayegh from Harvard Medical School discusses the potential harnessing of this "designer" approach for the prevention or cure of autoimmune diabetes.

TITLE: Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist