To understand how the immune system manages to disarm potentially harm
ful T cells with reactivity against self-antigens, many immunologists
have turned to model systems in which transgenic expression of TCRs, f
oreign antigens, or both, allows visualization of otherwise undetectab
le mechanisms. Recent data have offered several new insights into the
variables that dictate the mechanism for tolerance employed by periphe
ral T cells. Some of these mechanisms can also dampen ongoing immune r
esponses against foreign antigens and provide a strikingly powerful su
pplement to the primary mechanism of tolerance, thymic clonal deletion
.