We discovered and have characterized a unique T cell inhibitory pathway composed of DC-HIL on antigen presenting cells (APC) and its ligand syndecan- 4 (SD-4) on activated T cells. This pathway is distinguished by its ability to deactivate effector/memory T cells while sparing regulatory T cells. Our proposal will: elucidate signals within T cells triggered by DC-HIL/SD-4 ligation;develop strategies employing toxin-bearing DC-hIL to treat SD4+ T cell-mediated skin inflammation;and validate the differential effect of DC-HIL on effector vs. regulatory Tcells in vivo. Our new findings should lead to application of the DCHIL/ SD-4 pathway for biologic and/or pharmacologic benefit. Public