Immune suppressants may curb diabetes

YALE (US) — A new study has uncovered how targeted suppression of the immune system may prevent type 1 diabetes or induce sustained remission.

Type 1 diabetes is an autoimmune disease—the immune system goes into overdrive and attacks the body’s normal cells instead of foreign invaders. In type 1 diabetes, the immune system targets and eventually destroys the insulin-producing beta cells of the pancreas, leading to increased levels of blood sugars.

Researchers have undertaken clinical trials to study whether suppressing the inflammatory response of the immune system can prevent such misguided attacks. The monoclonal antibody teplizumab (anti-CD3) is currently being tested in clinical trials for prevention of type 1 diabetes and treatment of new-onset diabetes.


Although early data has been encouraging, the mechanism by which teplizumab might work has not been understood, until now.

Working with a mouse model with a functional human immune system, Yale University researchers focused on the effect of teplizumab on CD3-positive immune cells, which are key to the development of type 1 diabetes.

They found teplizumab induced the immune system’s T cells to migrate from the circulatory and lymph systems to the small intestine, where they produced the anti-inflammatory protein interleukin-10.

“When these cells returned to circulation, they had become regulators of the immune response,” says study author Kevan Herold, professor of immunobiology.

Co-author Richard A. Flavell, professor of immunobiology, led a study published last summer that defined the mechanism by which anti-CD3 drugs work in mice. “In this new study, we address the way this investigational drug works on human cells in a mouse model,” Flavell says. “The results are exciting and predictive of how this compound would work in people.”

The Yale research, published in the journal Science Translational Medicine, opens the way for further clinical trials that may explore the extent to which such targeted immunosuppression in humans may prevent the onset of type 1 diabetes or restore insulin-producing capability in early-onset patients.

“This study demonstrates how translational medicine can work for the benefit of patients,” adds author Frank Waldron-Lynch, M.D., clinical fellow in endocrinology.

This study was funded by grants from the Juvenile Diabetes Research Foundation, the Health Service Executive of Ireland, and the Yale Clinical and Translational Science Award from the National Center for Advancing Translational Sciences at the National Institutes of Health.

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