All cells of the immune system differentiate from multipotent haematopoietic stem cells; therefore, they must pass through multiple developmental checkpoints at which cell-fate decisions are made. In the T-cell lineage, immature CD4+CD8+ double-positive T cells must commit to either the CD4 or the CD8 lineage. As described by Ronald Germain, CD4- versus CD8-lineage commitment has been the focus of much study, often with contradictory results. Germain clears up some of the confusion and explains our current understanding of how this lineage decision is made.
Developmental decisions in the B-cell lineage are the focus of a Review by Flavius Martin and John Kearney, as well as a Highlight. Until recently, marginal-zone B cells were a poorly characterized B-cell subset, but transgenic and gene-targeted mouse models are now allowing us to understand how these cells are generated and their role in early immune responses.
As for marginal-zone B cells, the function of γδ T cells has remained elusive. Simon Carding and Paul Egan discuss how studies of infectious and autoimmune disease models are providing us with clues as to the biological functions of this heterogeneous group of T cells.
The Perspectives section of this issue focuses on therapies for inflammatory diseases. Marc Feldmann outlines how antibodies that are specific for tumour-necrosis factor have been developed into a highly effective therapy for rheumatoid arthritis and other inflammatory diseases. A Science and Society article from Mohan Sopori describes the effects of cigarette smoke on the immune system, concluding with a discussion of the possible anti-inflammatory therapeutic potential of nicotine.