Discrimination between self and non-self by the immune system is an essential prerequisite for eliminating foreign pathogens while ignoring the body's own constituents. Self-tolerance of autoreactive T cells occurs during development in the thymus (central tolerance); however, those T cells that escape thymic tolerance and enter the periphery are controlled by peripheral-tolerance mechanisms. Two reviews in this month's issue discuss the factors that are involved in establishing tolerance to self. On page 688, Bruno Kyewski and Jens Derbinski describe how our view of central tolerance has changed in the light of studies showing that tissue-restricted self-antigens are also expressed by thymic epithelial cells. And on page 665, Thomas Malek and Allison Bayer review the data supporting a crucial role for interleukin-2 in peripheral tolerance through its stimulation of regulatory T-cell production in vivo.

Most immunologists strive ultimately towards the generation of therapy for human disease, and this is reflected in several reviews this month. Adriano Aguzzi and Christina Sigurdson (page 725) explain that current therapeutic strategies for human prion diseases include those that either destroy prions or inhibit their replication. On page 699, Hiroshi Kiyono and Satoshi Fukuyama explain how the development of nasal vaccines will be facilitated by a clearer understanding of the differences between immune responses induced in the nasopharynx-associated lymphoid tissue and other lymphoid tissues.

Finally, the recruitment of T cells to the airways is crucial in asthma pathogenesis and is thought to be mediated mainly by chemokines. However, Andrew Luster and Andrew Tager (page 711) review the recent evidence indicating that lipid mediators, such as leukotrienes and prostaglandins, are also important and cooperate with chemokines in T-cell migration.