A two-signal model for T cell trafficking.

T-cell-receptor triggering and the delivery of co-stimulation are essential events leading to T cell expansion, differentiation and effector function. The influence that such signals exert on T cell migration during and following priming has been highlighted by recent reports. Moreover, induction of peripheral tolerance might act in part by affecting T cell migration. Here, we propose that the integration of co-stimulatory signals, which regulate the ability of primed T cells to access nonlymphoid tissue, and cognate recognition of the endothelium, which determines the selective recruitment of specific T cells, contribute to the anatomy of T cell-mediated immunity and tolerance. The implications for therapeutic strategies manipulating these signals are discussed.