Lupus Manifestations in Severe Combined Immunodeficient (SCID) Mice and in Human/Mouse Radiation Chimeras

被引:0
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作者
Zev Sthoeger
Heidy Zinger
Benny Dekel
Fabian Arditi
Yair Reisner
Edna Mozes
机构
[1] The Weizmann Institute of Science,Department of Immunology
[2] Kaplan Hospital,Department of Medicine “B,”
来源
Journal of Clinical Immunology | 2003年 / 23卷
关键词
Models of lupus; SCID mice; human/mouse radiation chimera; dsDNA specific autoantibodies; glomerular human IgG deposits;
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摘要
The objective of this study was to develop a human lupus model. To this end we have established and compared two models: (1) severe combined immunodeficient (SCID) mice reconstituted with peripheral blood lymphocytes (PBL) of either systemic lupus erythematosus (SLE) patients or healthy controls and (2) lethally irradiated BALB/c mice radioprotected with bone marrow of SCID mice, to which human PBL were transferred (human/mouse chimera). Engraftment was successful in most (78.4%) recipient mice as determined by the levels of human IgG measured. In about 50% of either SCID mice or human/mouse chimeras that were successfully engrafted with PBL of SLE patients, significant anti-dsDNA autoantibodies, mostly of the IgG1 and IgG2 isotypes, were determined. Interestingly, in a significant number (84.5%) of recipients of PBL of the healthy controls, anti-dsDNA antibodies were observed as well, suggesting that PBL of at least some of the healthy controls have the potential to develop SLE-associated autoantibodies under the appropriate stimulatory conditions. Glomerular immune deposits (human IgG, mouse C3) were detected in 70–80% of SCID mice with human DNA specific antibodies and in a third of the human/ mouse chimeras. Thus, SLE serology and glomerular pathology were reproducibly demonstrated in two models of human SLE. These models should allow the evaluation of potential therapies for the treatment of lupus patients.
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页码:91 / 99
页数:8
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