1. A New Strategy for Treatment of Autoimmune Diseases in Chimeric Resistant MRL/lpr Mice
by Kenji Takeuchi, Muneo Inaba, Shigeo Miyashima, Ryokei Ogawa, and Susumu Ikehara
Blood
Volume 91(12):
June 15, 1998
©1998 by American Society of Hematology

2. Experimental protocols.
Experimental protocols. Experimental protocol 1: Female MRL/lpr mice (3 to 4 months of age) with autoimmune diseases were irradiated (8.5 Gy) and transplanted with T-cell–depleted BMCs plus bone graft of B6 mice. Experimental protocol 2: Female MRL/lpr mice with autoimmune diseases were intraperitoneally injected with 100 mg/kg CY and then lethally irradiated (5 Gy × 2 = 10 Gy for 4-hour interval) 1 day later. Four hours after the second irradiation, the bones of the B6 mice, from which the BMCs had been flushed out, were engrafted under the subcutis of the MRL/lpr mice, and the mice received 5 × 107 WBMCs from B6 mice. One day after the first BMT plus bone graft, the mice were further transplanted with B6 WBMCs (5 × 107 cells).
Kenji Takeuchi et al. Blood 1998;91:
©1998 by American Society of Hematology

3. Survival rate in 6 groups.
Survival rate in 6 groups. Numbers in parentheses are numbers of mice in each group. Treatment of mice is shown in the figure. Statistical analyses were performed by a logrank test, and asterisks (**) represent the P values of treated (CY/2X/Bone/2BMT) versus other groups; **P < .01, *statistical insignificance.
Kenji Takeuchi et al. Blood 1998;91:
©1998 by American Society of Hematology

4. Autoantibodies in MRL/lpr mice treated with CY/2X/Bone/2BMT (Experimental protocol 2).
Autoantibodies in MRL/lpr mice treated with CY/2X/Bone/2BMT (Experimental protocol 2). RFs and anti-ss DNA Abs were measured at 48 weeks after the treatment (64 weeks of age). Autoantibodies in normal C57BL/6 and untreated MRL/lpr mice were measured at 18 weeks of age. The results are expressed as the mean ± SD at 405 nm from 5 mice. Asterisks (* and **) represent Pvalues of treated versus untreated MRL/lpr mice; *P < .005 and **P < .001.
Kenji Takeuchi et al. Blood 1998;91:
©1998 by American Society of Hematology

5. Immunofluorescence microscopical findings of glomerular IgG deposits in the kidneys of (A) untreated MRL/lpr at 18 weeks of age and (B) MRL/lpr mice treated with CY/2X/Bone/2BMT (56 weeks after the treatment [72 weeks of age]).
Immunofluorescence microscopical findings of glomerular IgG deposits in the kidneys of (A) untreated MRL/lpr at 18 weeks of age and (B) MRL/lpr mice treated with CY/2X/Bone/2BMT (56 weeks after the treatment [72 weeks of age]). The glomerulus of an untreated MRL/lpr mouse shows the IgG deposit, whereas the glomerulus of the treated mouse shows no IgG deposit.
Kenji Takeuchi et al. Blood 1998;91:
©1998 by American Society of Hematology

6. Histopathologic findings in the hindpaw joint of (A) untreated MRL/lpr at 18 weeks of age and (B) MRL/lpr mice treated with CY/2X/Bone/2BMT (56 weeks after the treatment [72 weeks of age]).
Histopathologic findings in the hindpaw joint of (A) untreated MRL/lpr at 18 weeks of age and (B) MRL/lpr mice treated with CY/2X/Bone/2BMT (56 weeks after the treatment [72 weeks of age]). The joint of the untreated MRL/lpr mouse shows marked lymphoid cell infiltration and pannus formation, whereas the joint of the treated MRL/lpr mouse shows neither lymphoid cell infiltration nor pannus formation.
Kenji Takeuchi et al. Blood 1998;91:
©1998 by American Society of Hematology

7. Histopathologic findings in the spleen (A), bone marrow (B), liver (C), colon (D), skin (E), and lung (F) of mice reconstituted with CD4-depleted BMCs [CY/2X/Bone/2BMT(−CD4)].
Histopathologic findings in the spleen (A), bone marrow (B), liver (C), colon (D), skin (E), and lung (F) of mice reconstituted with CD4-depleted BMCs [CY/2X/Bone/2BMT(−CD4)]. Histopathologic examination was performed 40 weeks after the treatment. The spleen and bone marrow show normal architecture with normal hematopoiesis, and there is no remarkable lymphocyte infiltration in the liver, colon, skin, or lung, indicating no GVHD.
Kenji Takeuchi et al. Blood 1998;91:
©1998 by American Society of Hematology