| OBJECTIVE To determine the effect of TACI-Ig, a recombinant fusion protein that modulates B cell activation by binding and neutralizing B lymphocyte stimulator (BlyS), on MRL-lpr mice and the mechanism of the effect.METHODS MRL/lpr mice were treated with TACI-Ig (3.75, 7.5, 15mg·kg-1), IgG-Fc (7.5mg·kg-1) (subcutaneously once every other day) and prednisone (5mg·kg-1) (intragastrically once a day) respectively and continuously for 8 weeks. Serum anti-dsDNA, ANA, IgG1, IgG2a levels were tested by enzyme-linked immunosorbent assays (ELISA). Thymus index and spleen index (the weight of thymus/spleen per 100g animal weight) were detected. Histopathological examination of lymphonode and spleen was observed by haematoxylin and eosine (HE) staining. Thymo-lymphocyte and spleno-lymphocyte proliferation were tested by 3H-TdR incorporation method. Splenic B cell subsets and lymphonode T cell subsets were analysed by flow cytometry.RESULTS1. Effect of TACI-Ig on spleen and lymphonode pathologyTACI-Ig (7.5, 15mg·kg-1) subcutaneously treatment significantly improve the pathological of SLE-like changes in spleen and lymphonode and inhibited the spleen index.2. Effect of TACI-Ig on spleno-lymphocyte proliferation and thymo-lymphocyte proliferationTACI-Ig (7.5, 15mg·kg-1) subcutaneously treatment significantly inhibited spleno-lymphocyte proliferation induced by LPS.3. Effect of TACI-Ig on auto-antibodies in serumTACI-Ig (3.75,7.5,15mg·kg-1) subcutaneously treatment significantly supressed the elevated levels of ANA, anti-dsDNA, IgG1, IgG2a.4. Effect of TACI-Ig on T, B lymphocyte subsets and function.The percentage of CD19+ B cells, CD19+IgD+ B cells, CD19+IgM+ B cells in spleen of MRL-lpr mice also decreased significantly, with no significant change in CD19+CD21+ B cells, CD19+CD23+ B cells, CD19+CD27+ B cells.The percentage of CD4+CD25+ T cells increased and the percentage of CD4+CD69+ T cells decreased.CONCLUSIONS1. TACI-Ig can improve the pathological of SLE-like changes in spleen and lymphonode in MRL/lpr mice and low the levels of autoantibodies, It has an apparently treatment effects on MRL/lpr mice.2. TACI-Ig can inhibit spleno-lymphocyte proliferation and effect the percentage of T, B lymphocyte subsets. It can regulate the disnomal function of immunity in MRL/lpr mice. |
PDF Full Text Request