Figure 2.

Model for type 1 diabetes as a relapsing-remitting disease. (A) Graph showing the stepwise, nonlinear decline of β-cell mass over time, as well as the development of autoantibodies that are associated with hyperglycemia, that is, the onset of T1D. (B) The immunological response to T1D is cyclic. An increase in the numbers of autoreactive effector T cells is controlled by an increase in the number of regulatory T cells. However, over time, a gradual disequilibrium of the cyclical behavior could occur, leading to the number of autoreactive effector T cells surpassing the number of regulatory T cells, which would no longer be capable of containing autoreactive effector T-cell responses and thereby lead to a decline in pancreatic islet function. (C) β-Cell proliferation increases in a cyclical fashion over time. This figure indirectly depicts the biological trends of the development of T1D, which may be attributed to the cyclical nature of the immunological events that lead to the attack or protection of β cells. Such a phenomenon is usually the result of feedback-loop mechanisms, which, in the case of T1D, could be due to misdirected effector T cells that are not easily controlled by regulatory T cells. The inflammatory process of the pancreatic islets themselves may enhance β-cell proliferation and antigenic presentation, ultimately leading to the generation of more effector and regulatory T cells. In addition, as β-cell mass declines, the pressure on each β-cell to produce insulin increases, which may be sufficient to alter the recognition of β cells by the immune system and to alter their ability to regenerate and increase insulin production. (Adapted from von Herrath et al. 2007; with permission.)