Fig. 4.
Conditioning with anti-CD3 and SAHA allowed induction of complete chimerism and reversed severe glomerulonephritis. Old NZB/W F1 mice (> 7 months) with severe proteinuria were conditioned with anti-CD3 and SAHA and transplanted with C57BL/6 donor BM (2 × 106/g) and CD4+ T-depleted spleen cells (4 × 106/g). The recipients were monitored for clinical signs of GVHD daily and body weight and proteinuria twice a week. The recipients were checked for chimerism 8 weeks after HCT. (A) Blood mononuclear cells of the anti-CD3 and SAHA-conditioned mice with or without HCT were stained for H-2b (donor marker) versus TCRαβ, B220, or Mac-1/Gr-1. The percentage of donor-type T, B, and macrophage cells is shown. One representative of 10 mice in each group is shown. (B) Body weight change curves of the mice given conditioning alone or conditioning and HCT over a 180-day period after HCT. Mean ± SE of 10 mice in each group is shown. (C and D), Proteinuria change curve and survival curve of the lupus mice given conditioning alone or conditioning and HCT. (E) Kinetic changes of serum levels of anti-dsDNA IgG2a antibodies in lupus mice given conditioning and HCT. (F) Hematoxylin/eosin staining of kidney tissues and immunofluorescent staining of IgG deposition in glomeruli of the lupus mice before treatment and 180 days after HCT. One representative sample of four examined mice in each group is shown.