2002 年 54 巻 2-4 号 p. 136-149
We have succeeded in treating intractable autoimmune diseases in chimeric resistant MRL/lpr mice by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation (5.5 Gy x2) followed by intra-bone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C 57 BL/6 (B 6) mice [5.5 Gy X2+ IBM]. In MRL/Ipr mice treated with this method, the number of not only donor-derived cells but also donor-derived hemopoietic progenitor cells increased. Furthermore, donor-derived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with [5.5 GyX2+IBM]. All the recipients thus treated survived more than one year (60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (Thy 1.2+/B 220k+CD 4-/CD 8-) disappeared. These findings clearly indicate that this new strategy (IBM-BMT) creates the appropriate hemopoietic environment for the early recovery of hemopoiesis and donor cell engraftment, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants. This strategy would therefore be applicable to human therapy.
