Credit: Reprinted with permission of Cell Press

Despite their growing fame, very little is known about how regulatory T cells (Tregs) generate immunological tolerance. Thorsten Mempel, Mikael Pittet and colleagues examined the activity of these cells in vivo, using real-time imaging in mice.

The investigators reported that Tregs seem to operate by preventing cytotoxic 'killer' T cells (CTLs) from releasing the deadly contents of cytolytic granules (Immunity 25, 129–141). Shown is a cytotoxic T cell (green) raised in an environment with Tregs. This CTL engaged an antigen-presenting B cell (purple) and followed it around for 14 minutes, indicating that regulated CTLs can interact with their targets. Eventually the CTL disengaged and the B cell carried on (not shown; for movies, go to http://cmir.mgh.harvard.edu/cip/cip_research_cancer_2.php?menuID_=367). The researchers found that nonregulated CTLs killed their targets 6.6 times faster than regulated CTLs—which are slow to release the contents of their granules.

Consistent with previous findings, transforming growth factor-β was found to be necessary for the suppressive activity of Tregs. Tregs themselves are an unlikely source of this cytokine, but in Nature (doi:10.1038/nature05010), Li-Fan Lu et al. speculate that mast cells might be one source. The researchers report that mast cells, best known for their proinflammatory role in allergic disorders, seem to mediate the generation of tolerance by regulatory T cells.