Generation of biliary lesions after transfer of human lymphocytes into severe combined immunodeficient (SCID) mice

S. M. Krams, K. Dorshkind, M. Eric Gershwin

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

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 immunodeficiency 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 106 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 the 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.

Original languageEnglish (US)
Pages (from-to)1919-1930
Number of pages12
JournalJournal of Experimental Medicine
Volume170
Issue number6
DOIs
StatePublished - 1989

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SCID Mice
Biliary Liver Cirrhosis
Lymphocytes
Bile Ducts
Dihydrolipoyllysine-Residue Acetyltransferase
Serum
Severe Combined Immunodeficiency
Injections
Autoantigens
Biliary Tract
Autoimmune Diseases
Healthy Volunteers
B-Lymphocytes
Necrosis
Spleen
Animal Models
Immunoglobulin G
Tissue Donors
Inflammation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Generation of biliary lesions after transfer of human lymphocytes into severe combined immunodeficient (SCID) mice. / Krams, S. M.; Dorshkind, K.; Gershwin, M. Eric.

In: Journal of Experimental Medicine, Vol. 170, No. 6, 1989, p. 1919-1930.

Research output: Contribution to journalArticle

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