How Does B-Cell Tolerance Contribute to the Protective Effects of Diabetes Following Induced Mixed Chimerism in Autoimmune Diabetes?

  1. F. Susan Wong
  1. Institute of Molecular and Experimental Medicine, Cardiff School of Medicine, Cardiff University, Cardiff, U.K.
  1. Corresponding author: F. Susan Wong, wongfs{at}cardiff.ac.uk.

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 …

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