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Journal of Experimental Medicine, Vol 170, 1919-1930, Copyright © 1989 by Rockefeller University Press
ARTICLES |
SM Krams, K Dorshkind and ME Gershwin
Department of Internal Medicine, University of California, Davis 95616.
Human PBL have been reported to reconstitute B and T cells as well as human serum Ig in mice with severe combined immunodeficiency disease (SCID). To confirm these observations and attempt the transfer of an autoimmune disease to the immunodeficient animals, groups of SCID mice received an injection of PBL from patients with primary biliary cirrhosis (PBC) or from normal volunteers. By 8 wk after the injection of 10-42 x 10(6) PBL into the mice, human lymphoid cells were detected in the spleen of approximately half of the animals and all had detectable serum levels of human IgG. Moreover, the sera of SCID mice that received cells from patients with PBC contained human antimitochondrial antibodies (AMA) to dihydrolipoamide acetyltransferase, the major mitochondrial autoantigen of PBC. Histologically, a human mononuclear cell infiltrate was present around the portal areas of the liver and inflammation, bile duct atypica, and necrosis of bile duct cells were observed. While the biliary lesions in the SCID recipients of PBC cells were more severe, a mononuclear infiltrate was clearly evident in mice that received cells from normal donors, suggesting the presence of a graft-vs.-host-like disease. While these data are the first to describe an animal model with both the humoral and cellular characteristics of PBC, they also raise an interesting question regarding the preferential localization of lymphoid cells to the biliary system.
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