No abstract

These observations suggest that there is a good correlation between urinalysis and histopathological events of SCG/Kj mice, and that endocapillary proliferation, which contains neutrophil infiltration, may contribute to the subsequent crescent formation in these mice.

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Female MRL/lpr mice develop lesions closely resembling human systemic lupus, and therefore can serve as modelsin order to examinethe efficacy of immunosuppressive agents. The present study was designed to evaluate the efficacy of the combination of deoxyspergualin with prednisolone compared with each alone in 1 3-week-old female MRL/lpr mice. After the onset oflymphadenopathy, splenomegaly, and the elevation of plasma autoantibodies, deoxyspergualin alone or prednisolone alone was effective. Animmunosuppressive regimen of deoxyspergualin combined with prednisolone was demonstrated to be superior to each single therapy concerning the amelioration of advanced disease in the MRL/lpr mice without increasing toxicity.

Both MRL-lpr/lpr (lpr) and BXSB mice fall victim to autoimmune disease as a function of age. To combine their properties, brother-sister mating of (female lpr x male BXSB)F1 mice was done. Mice for mating were selected according to indicators of early onset of glomerulonephritis and subsequent early death (i.e., EOD). This mating was continued for more than 16 generations. The EOD mice thus established had homozygous H-2k/k, lpr/lpr, and possible yaa/- (in the case of males). The average life span of males was 83 days while that of females was 126 days. After 12 weeks of age, the majority (> 80%) of male EOD mice were characterized by the abnormality of urine due to glomerulonephritis. We then characterized how glomerulonephritis was evoked, especially in terms of expanding lymphocyte subsets in various immune organs. Similar to the case of parental lpr mice, the major expanding cells were CD4-8-B220+ TCRint cells in the immune organs and kidney. In addition, myeloid cells were found to infiltrate the kidney. This massive infiltration of both TCRint cells and myeloid cells might be responsible for the onset of acute glomerulonephritis. Even after more than 50 generations, these EOD mice still carry both lpr and yaa genes. These results suggest that EOD mice might be a very useful tool for the study of acute lupus glomerulonephritis which is evoked by the genetic abnormalities.