Therapeutic manipulation of T cell chemotaxis in transplantation.

T cell migration and trafficking are regulated by the well defined cellular processes of rolling, activation, tight adhesion, arrest and diapedesis. These processes are, in turn, controlled by molecular events involving integrins, selectins, chemokines and chemokine receptors. Recent studies have shown that sphingosine 1-phosphate receptors and their ligands are also important molecular modulators of migration and trafficking. Many of these molecules are appropriate targets for preventing allograft rejection or for achieving tolerance. Studies of migration and trafficking have also shown that the anatomic choreography of alloantigen presentation and T cell encounter with alloantigen and immunosuppression, are over-riding determinants of T cell priming versus tolerization.