How Does B-Cell Tolerance Contribute to the Protective Effects of Diabetes Following Induced Mixed Chimerism in Autoimmune Diabetes?
- Institute of Molecular and Experimental Medicine, Cardiff School of Medicine, Cardiff University, Cardiff, U.K.
- Corresponding author: F. Susan Wong, .
In type 1 diabetes, autoimmune-mediated damage and destruction of insulin-producing β-cells lead to a raised blood glucose. Glucose itself is toxic and some recovery of β-cell function is expected in the honeymoon phase after insulin treatment is instituted, but it was previously believed that all β-cells will ultimately be lost. In fact, there are individuals who continue to have some functioning β-cells, even many years after the onset of type 1 diabetes (1,2). This raises the hope that treatment to induce replication or regeneration of β-cells could be instituted in patients with long-standing diabetes, and makes it even more imperative that means of halting autoimmunity are found.
Although nonmyeloablative autologous stem cell transplantation has been carried out, with long-term insulin independence successfully achieved in type 1 diabetes (3,4), many would feel that the risk-benefit ratio of this treatment is not acceptable for general use. Many other strategies, both nonantigen- and antigen-specific therapies, have been trialed in patients with new-onset type 1 diabetes, but none, as yet, has provided a long-term solution to the autoimmune attack on remaining β-cells (5). However, short-term slowing of β-cell loss was seen with T-cell−targeted therapy using nondepleting anti-CD3 (6,7), which was shown to temporarily reduce T cells, but, more importantly, to increase T-cell regulation. In addition, anti-CD20 treatment (rituximab) that targets B cells also temporarily slowed loss of endogenous insulin production (8,9 …