E3

of protection against intruders and quenching any local disturbances. Under certain stimulatory conditions, additional members of the department can be recruited into active duty, affording a more potent protective police force. It is only under the most unusual combination of circumstances where such protective T cells are corrupted into criminal behavior that results in tissue destruction and true autoimmune disease. I hope that the readership will consider the merits (and the shortcomings) of this conceptual framework and I look forward to your thoughts and to your feedback.

Acknowledgements

I wish to especially thank Rob Fairchild, Anna Valujskikh and Charley Orosz for their helpful discussions, input and feedback.

This article is reprinted from Graft 2003; Vol. 6, No. 1:33-41, with permission from the authors.

References

1. Jameson SC, Hogquist KA, Bevan MJ. Positive selection of thymocytes. Annu Rev Immunol 13:93.

2. Sha WC, Nelson CA, Newberry RD et al. Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature 1988; 336:73.

3. Kisielow P, Teh HS, Bluthmann H et al. Positive selection of antigen-specific T cells in thymus by restricting MHC molecules. Nature 1988; 335:730.

4. von Boehmer H, Teh HS, P. Kisielow P. The thymus selects the useful, neglects the useless and destroys the harmful. Immunol Today 1989; 10:57.

5. Targoni OS, Lehmann PV. Endogenous myelin basic protein inactivates the high avidity T cell repertoire. J Exp Med 1998; 187:2055.

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