T-Cell-Directed Treatment Strategies for Type 1 Diabetes and the Confounding Role of Inflammation

Abstract

Described by Arataeus as “a melting down of flesh and limbs into urine”, the etiology of diabetes long remained a mystery. From the time of Arataeus, approximately 3500 years passed until the disease was controversially linked, at least initially, to malfunction of the pancreas and soon thereafter linked to a failure to produce insulin. The discovery of insulin and the availability of insulin as a therapy changed the fate of millions of patients affected by this condition; however, treatment with exogenous insulin does not provide patients with Type 1 diabetes mellitus (T1DM) protection from long-term morbid complications. In humans and nonobese diabetic (NOD) mice with T1DM, autoimmune T cells infiltrate and destroy insulin-producing β-cells, thereby creating an insulin-deficient state [1]. The hypothesis that pancreas transplantation or, even better, transplantation with insulin-producing β-cells harvested from pancreatic islets represents a better therapeutic solution than exogenous insulin treatment was successfully tested by Paul Lacy [2,3]. Since islets possess both glucose sensors and insulin-secreting cells, tight control of hyperglycemia can often be established with a successful transplant.