Inhibition of Tolerance

Kretz-Rommel and Rubin found that injection of the reactive metabolite of procainamide into the thymus of mice leads to autoantibodies against chromatin (KretzRommel et al. 1997). Furthermore, transfer of T cells from one animal to another resulted in autoantibodies in the recipient mice (Kretz-Rommel and Rubin 1999). It has been proposed that this response is due to a failure in the normal development of tolerance in autoantigens. Although the amount of reactive metabolite was relatively small, the local concentration is likely to have been much higher than that produced in vivo and to kill cells in the area of injection. An important control experiment would be to inject some other caustic agent or even to use a hot needle to kill an area of cells in the thymus to see whether this would result in a similar syndrome that is unrelated to specific effects of procainamide.

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