A band of ICAM-1 (red) bound to the integrin LFA-1 helps T cells move quickly.

The well-described mechanism of movement by fibroblasts and other flat cells is characterized by outstretched lamellipodia, which are attached through focal adhesions, and retraction of a trailing edge. But how lymphocytes move up to 100-times faster has been unclear. On page 141, Smith et al. report that T cells have a zone of clustered high-affinity LFA-1 integrin (αLβ2) at the midzone of the cell, and that disruption of the pattern by removal of talin reduces the speed of cell migration.

When T cells contact a monolayer of cells expressing ICAM-1, activated LFA-1 concentrates in the midzone of the cells, a region that the researchers referred to as the “focal zone.” The concentrated active LFA-1 in this focal zone colocalized with bound ICAM-1 in the supporting cells. Furthermore, the LFA-1 was unable to diffuse freely and was found to interact with the cytoskeleton via the cytoskeletal linker protein talin. An siRNA knockdown of talin destabilized the LFA-1 focal zone and slowed T cell migration.

By contrast, interference reflection microscopy showed that the lamellipodia made intermittent contacts with ICAM-1, but did not contain high-affinity, clustered LFA-1. The trailing edge uropod, which was not in contact with the underlying cells but was rather held in the air above them, also contained significant quantities of LFA-1, but this LFA-1 was not active.

Based on these data, the researchers conclude that T cells use a novel mode of migration that depends on an interaction between the localized integrin LFA-1 and ICAM ligand expressed by neighboring cells. The focal zone type of movement lacks stable lamellipodial or uropodial attachments. Smith et al. speculate that without these constraints—or the time it takes to make or break them—lymphocytes can move more rapidly than firmly attached cells. If that is true, then one might expect other rapidly migrating cells, such as neural crest cells, to display a concentrated band of ligand-binding integrin at their midsection.