Activating a subset of myelin basic protein (MBP)-specific T cells that have escaped tolerance induces autoimmune encephalomyelitis in mice. This is considered a disease model for multiple sclerosis. Escaping tolerance is believed to result from sequestration of MBP within immune-privileged sites that allow only limited lymphocyte trafficking. In the April Immunity Eric Huseby and colleagues from University of Washington, Seattle show that escaping tolerance is also an age dependent mechanism.

Huseby et al constructed transgenic mice specific for MBP121-150 and studied their fate in MBP-/-, MBP+/-, and MBP+/+ at different stages of development. They found that efficiency of tolerance is age dependent, reflecting the developmentally regulated expression of MBP. Dependence of tolerance on the amount of MBP expressed in vivo results in an age window of maximum susceptibility to encephalomyelitis in mice during puberty (Immunity 2001, 14:471-481).

These results suggest that genetic...

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