Antigen-specific CD8+ OT1 Teff cell–mediated destruction of OVA+ islets and concomitant growth of juxtaposed bystander OVA− islets. (Corresponds to Fig. 3.) Gray mass, OVA+CFP− islet; blue mass, OVA−CFP+ bystander islets; green, CD8+ OT1 Teff cells. QuickTime Virtual Reality (QTVR) movies showing 3D view of “conjoined” (juxtaposed) OVA+ (gray; visualized by laser backscatter) and CFP-labeled OVA− islets (blue) in the ACE of recipient mouse on day 3 after reconstitution with 1–2 × 106 activated GFP-labeled CD8+ OT1 Teff cells (green). QTVR movies allow XYZ rotation and zoom by the user to examine the islet structure in 3D. On day 3 after T cell transfer, intact OVA+ islet is clearly visible on top of the iris (gray; visualized by backscatter) with no evident T cell infiltrate; in the ensuing days, however, CD8+ OT1 Teff cells appeared within the graft coinciding with significant damage and complete destruction by day 7 after transfer. In contrast, juxtaposed CFP-labeled OVA− islet was not subject to bystander damage; rather, CFP-labeled β cell mass significantly increased, likely due to β cell proliferation. Video represents imaging of four pairs of conjoined islets in three mice.
