Objective: To establish the murine systemic lupus erythematosus (SLE) model of chronic graft versus host diseases(cGVHD). To analyze the pathological changes and serological and immunological features in the animals.
Methods: Female (C57BL/10 x DBA/2)F1 hybrids aged 6-8 weeks were randomly divided into model group and healthy controls (HC). Lymphocytes from female DBA/2 were injected intravenously to the model group on days 0, 3 and 8, while PBS were injected to the HC under the same condition as a control group. Bradford was applied to monitor the development of albuminuria quantitively. Sera were tested by enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) for the presence of autoantibodies. To compare the differences of CD4+ CD25+ Treg cells between the two groups by flow cytometry (FCM) and the differences in the expression of Foxp3 by real time polymerase chain reaction(RT-PCR). The kidneys of model mice were removed in the 12th week and were made frozen sections for direct immunofluorescence(DIF)and paraffin imbedding for PASM staining.
Results: The titers of proteinuria in model group in the 6th week, 8th week, 10th week, and 12th week were significantly higher than those of the HC groups(P=0.004, 0.005,respectively). The titers of anti-dsDNA and anti-nucleosome antibodies were significantly increased in the model group compared with the HC (P<0.05). And the positive rates curves of ANA, anti-dsDNA Abs and anti-nucleosome Abs in model group were significantly different from those of control group (P<0.05). And The proportions of CD4+CD25+ regulatory T cells from peripheral blood of model group were significantly lower than those of control group (P=0.002), while the expression of Foxp3, one of the most important biomarkers of Treg cells, was not significant. There were mesangial matrix expansion and mesangial cell proliferation in the nephritic pathology in model group and the depositions of IgG along the glomerular capillary walls and in the mesangium were observed in model group. There were no pathological changes and depositions in HC group.
Conclusion: It has been proved that there are not only protienuria and autoantibodies, but also decrease of the regulatory T lymphocytes in murine model of cGVHD. All of these results suggest that the cGVHD murine SLE models were successfully established.