The mammalian immune system must specifically recognize and eliminate foreign invaders, but refrain from damaging the host itself. This task is accomplished in part by the production of a large number of T lymphocytes each bearing a different antigen receptor to match the enormous variety of antigens present in the microbial world. However, because antigen receptor diversity is generated by a random mechanism, the immune system must tolerate the function of T lymphocytes that by chance express a self-reactive antigen receptor. Therefore, during early development, T cells that are specific for antigens expressed in the thymus are physically deleted. The population of T cells that leaves the thymus and seeds the secondary lymphoid organs contains helpful cells that are specific for antigens from microbes, but also potentially dangerous T cells that are specific for innocuous extrathymic self antigens. The outcome of a peripheral T cell's encounter with these two types of antigens is to a great extent determined by the inability to naive T cells to enter non-lymphoid tissues, or to be productively activated in the absence of inflammation.

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1998-1999 Mathematics in Biology