Chemokines were known to costimulate T cell activation in vitro and up-regulate integrins that might slow down the T cells. But chemokines in solution also induced T cell migration past a surface laden with stimulatory T cell receptors (TCRs).
This “paradox,” says Krummel, is resolved by the new data. He thinks the T cells bind APCs and then move arm over arm, “like swinging on monkey bars.” The San Francisco group found that T cells contacted, crawled along, and then attempted to crawl away from chemokine-laden APCs. For some time, however, they remained tethered to the APC due to chemokine-induced signaling in the T cell.
The leading edge of these tethered cells projected out in search of an APC surface and was faster at forming an immunological synapse than if chemokine stimulation had never happened. The mechanism behind this improvement is unknown, but polarization of the T cell is probably involved, and the mechanism worked even if the eventual target APC did not itself have bound chemokines.
“You used to think T cells were drawn into a cavity and once there they had to fend for themselves,” says Krummel. The new results “accentuate the idea of the microenvironment” in which T cell movements are tightly choreographed within the lymph node.