Failure to induce organ-specific autoimmunity by breaking of tolerance: importance of the microenvironment
✍ Scribed by Andreas Limmer; Torsten Sacher; Judith Alferink; Marianne Kretschmar; Günter Schönrich; Thomas Nichterlein; Bernd Arnold; Günter J. Hämmerling
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 331 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Peripheral tolerance is considered to be a safeguard against autoimmunity. Using a TCR-transgenic mouse system displaying peripheral tolerance against a liver-specific MHC class I Kb antigen, we investigated whether the breaking of tolerance would result in autoimmunity. Reversal of tolerance was achieved by simultaneous challenge with cells expressing the Kb autoantigen and IL-2. Tolerance could not be broken with IL-2 alone or when Kb- and IL-2-expressing cells were applied to different sites of the mice. However, despite the presence of activated autoreactive T cells that were able to reject Kb-positive grafts no autoaggression against the Kb-positive liver was observed. These results indicate that breaking of tolerance per se is not sufficient to cause liver-specific autoimmunity. However, when in addition to breaking tolerance the mice were infected with a liver-specific pathogen, autoaggression occurred. Thus, in this system at least two independent steps seem to be required for organ-specific autoimmunity: reversal of peripheral tolerance resulting in functional activation of autoreactive T cells and conditioning of the liver microenvironment which enables the activated T cells to cause tissue damage.