Abstract
Intravital imaging is revealing immunological phenomena not predicted by in vitro studies. Pioneering in vivo imaging studies in lymph nodes have established cellular mechanisms crucial during immune defense of the organism. Such findings have primed therapies targeted at immune cells in the lymph nodes. However, immune responses in the non-lymphoid target tissues offer equally valuable therapeutic targets. Here we studied noninvasively the in vivo behavior of antigen-specific T[subeff]cells against beta-cell in intraocular pancreatic islet grafts. Our studies suggest that antigen-specific CD4[sup +] Tcells could kill target beta-cell through direct long-lasting contacts, a feature characteristic of cytotoxic CD8[sup +] T[subeff] cells (CTL). Together, our findings demonstrate the importance of contact dependent killing by antigen-specific CD4[sup +] T[subeff]cells, and highlight an unprecedented potential for "rapid" islet regeneration under specific conditions. Our results also show the potential role of direct T[subreg] - T[subeff] interactions within non-lymphoid target tissues in local immune modulation and tolerance induction.