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a First Department of Pathology,
b First Department of Internal Medicine, Kansai Medical University, Moriguchi-City, Osaka 570, Japan
Key Words. Hemopoietic stem cells • W/BF1 mouse • Bone marrow transplantation
Dr. Susumu Ikehara, 1st Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570, Japan.
The transplantation of partially purified hemopoietic stem cells (HSCs) plus the engraftment of bone from autoimmune-prone mice ((NZW x BXSB)F1 (W/BF1) mice) induces autoimmune diseases in major histocompatibility complex (MHC)-incompatible normal C3H/HeN mice. In contrast, W/BF1 mice die of infection or anemia within three weeks due to a failure in hemopoietic reconstitution when the mice receive partially purified HSCs plus bones from normal C3H/HeN mice, although they survive more than a year without showing any symptoms of autoimmune diseases when they receive T cell-depleted bone marrow cells (without bone grafts) from normal mice. This finding suggests that abnormal HSCs can proliferate even in MHC-incompatible microenvironments, while normal HSCs cannot. This is confirmed by spleen colony-forming assays (CFU-S) on day 12, using pluripotent HSCs (P-HSCs). The P-HSCs of old (> 4 mo) W/BF1 mice (after the development of autoimmune diseases) form high CFU-S counts on day 12 even in the allogeneic C3H environment, although the P-HSCs of normal mice form high CFU-S counts only in the MHC-compatible environments. In addition, abnormal P-HSCs of autoimmune-prone mice can proliferate in vitro in collaboration with MHC-incompatible stromal cells, although normal HSCs do so in collaboration with MHC-compatible stromal cells, but not MHC-incompatible stromal cells. These findings indicate that abnormal P-HSCs are more "resilient" than normal P-HSCs.
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