PMID- 10688849 OWN - NLM STAT- MEDLINE DCOM- 20000329 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 95 IP - 5 DP - 2000 Mar 1 TI - Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation. PG - 1862-8 AB - A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PV + IV). All recipients survived more than 1 year after this treatment (more than 64 weeks after birth). Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells. The treated mice are free from autoimmune diseases. Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (Blood. 2000;95:1862-1868) FAU - Kushida, T AU - Kushida T AD - First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan. FAU - Inaba, M AU - Inaba M FAU - Takeuchi, K AU - Takeuchi K FAU - Sugiura, K AU - Sugiura K FAU - Ogawa, R AU - Ogawa R FAU - Ikehara, S AU - Ikehara S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Autoantibodies) RN - 8N3DW7272P (Cyclophosphamide) SB - IM MH - Animals MH - Autoantibodies/blood/immunology MH - Autoimmune Diseases/immunology/pathology/*therapy MH - Bone Marrow Transplantation/*methods MH - Cyclophosphamide/pharmacology MH - Dose Fractionation, Radiation MH - Female MH - Injections, Intravenous MH - Kidney/pathology MH - Lymphoproliferative Disorders/immunology/pathology/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C3H MH - Mice, Inbred C57BL MH - Mice, Inbred MRL lpr MH - Portal Vein MH - Radiation Chimera MH - Transplantation Conditioning/*methods MH - Whole-Body Irradiation/methods EDAT- 2000/02/26 09:00 MHDA- 2000/04/01 09:00 CRDT- 2000/02/26 09:00 PHST- 2000/02/26 09:00 [pubmed] PHST- 2000/04/01 09:00 [medline] PHST- 2000/02/26 09:00 [entrez] AID - S0006-4971(20)67039-2 [pii] PST - ppublish SO - Blood. 2000 Mar 1;95(5):1862-8.