Recent work has greatly increased our understanding of the immune function of two important organs — the spleen and the brain. On page 606, Reina Mebius and Georg Kraal discuss how the unique structure and location of the spleen allow it to coordinate innate and adaptive immune responses effectively, making it a crucial site for the initiation of responses to blood-borne pathogens. By contrast, the central nervous system (CNS) was originally thought to be an immune-privileged site, and it is only recently that inflammatory responses have been shown to take place in the brain. Nancy Rothwell and colleagues (page 629) discuss the role of the pro-inflammatory cytokine interleukin-1 in the CNS and its contribution to neurodegenerative conditions such as Alzheimer's disease.

Also in this issue, several articles focus on the theme of regulation in the immune system. Ke Shuai and Bin Liu (page 593) discuss the various mechanisms by which protein inhibitor of activated STAT (PIAS) proteins might regulate the expression of key transcription factors in the immune system, and they describe the specificity of PIAS proteins in regulating only a subset of cytokine-induced genes. Vincenzo Bronte and Paola Zanovello (page 641) discuss the more-global regulation of lymphocyte responses by myeloid suppressor cells, through metabolism of the amino acid L-arginine. As myeloid cells also metabolize L-tryptophan, through expression of indoleamine 2,3-dioxygenase (IDO), the authors suggest that amino-acid metabolism is a general strategy for limiting T-cell activation and proliferation. Finally, in an Opinion article, on page 655, Peter Lane and colleagues discuss their view that the CD4+CD3 cells that have previously been implicated in controlling lymphoid-tissue organization during development also have a role in regulating B-cell responses, through effects on T-cell survival.