TRANCE–RANK, a New Signal Pathway Involved in Lymphocyte Development and T Cell Activation

Almost a decade ago, major advancements in our understanding of the cell–cell interactions that were critically involved in the regulation of the immune response were achieved when it was established that T cell activation not only required a signal through the T cell receptor but also a second signal generated by the interaction of costimulatory molecules CD80 and CD86 on the surface of APCs and CD28 or CTLA-4 on T cells (1). Since then, identification of other molecular interactions that are important in regulating the immune response has increased dramatically, elucidating signals that enhance stable cellular interactions between APCs and T cells as well as apoptotic signals that regulate survival of either the APC or the T cell (2, 3). One molecular interaction that has received enormous attention is that between CD40 on APCs and CD154 on T cells (reviewed in 4). CD40–CD154...