CD8 CYTOTOXIC T-CELL CLONE RAPIDLY TRANSFERS AUTOIMMUNE DIABETES IN VERY YOUNG NOD AND MHC CLASS I-COMPATIBLE SCID MICE

A CD8 T-cell clone (YNK1.3) generated from acutely diabetic NOD mouse islets, showed proliferation and cytotoxicity when challenged with NOD and BALB/c islet cells and NOD-derived insulinoma cells. When 1-2 x 1 0(7) YNK1.3 cells were administered to 7-10-day-old NOD mice, the cell s transferred overt diabetes very rapidly in each of the 16 recipients within 4 days of cell transfer. However, of 14 recipients receiving Y NK 1.3 cells above 14 days of age none became diabetic. Fluorescent dy e-labelled YNK1.3 cells extensively accumulated in the islets by 36 h after transfer in 7-day-old NOD recipients, while no significant insul itis was seen in 21-day-old recipients. Over half of NOD-scid recipien ts (5/9) rapidly became diabetic within 5 days after transfer of 1-2 x 10(7) YNK1.3 cells at 7 days of age, whereas only one of 12 recipient s over 14 days of age became diabetic. Furthermore, YNK1.3 cells also transferred diabetes to H-2K(d)-matched very young BALB/c-scid and CB1 7-scid mice, but not to C57BL/6-scid mice. Thus, optimally activated i slet-specific CD8 T-cell clones are able to rapidly transfer diabetes to NOD and MHC class I compatible scid mice when a large enough number is administered at 7 days of age. Administration of monoclonal antibo dies against adhesion molecules involved in the trafficking of lymphoc ytes from the circulation into the inflammatory tissues, could not pre vent the cellular infiltration of YNK1.3 cells into the islets in 7-da y-old NOD recipients. The results indicate that islet cells in the mou se around 7 days of age are generally susceptible to cytotoxic CD8 T c ells, suggesting, therefore, that CD8 T cells may play an important ro le in the initiation of autoimmune diabetes in NOD mice.