Laboratory Investigation

Kidney International (1987) 32, 642–651; doi:10.1038/ki.1987.256

Induction, characterization, and cell transfer of autoimmune tubulointerstitial nephritis

Kym M Bannister1, Thomas R Ulich1 and Curtis B Wilson1

1Department of Immunology, Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California, USA

Correspondence: Curtis B Wilson MD, Department of Immunology (IMM5), Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California 92037, USA.

Received 11 February 1987; Revised 16 June 1987.

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Abstract

Induction, characterization, and cell transfer of autoimmune tubulointerstitial nephritis. Autoimmune tubulointerstitial nephritis (TIN) was induced in Lewis (LEW) rats by immunization with homologous Brown–Norway (BN) rat renal basement membrane (RBM), complete Freund's adjuvant and Bordetella pertussis vaccine. The BN strain has a tubular basement membrane (TBM) antigen (Ag+) detectable by immunofluorescence which is lacking in unmodified LEW rat TBM. Development of TIN in LEW rats correlated with TBM Ag+ immunogens from homologous and heterologous RBM preparations. By day 14 after immunization TIN developed characterized by elevated serum creatinine levels and by tubular destruction with focal, circumscribed lesions containing epithelioid cells, giant cells and mononuclear cell infiltrates. Approximately 60% of the mononuclear cells bore T cell antigens with most cells expressing la markers. Immunofluorescence and elution studies revealed no selective IgG fixation to TBM at day 14 despite high titers of circulating alloantibody reactive with the immunizing TBM. Intravenous transfer of LNC and/or splenic cells (3.5 to 7 times 108) to naive LEW rats resulted in less severe but histologically identical TIN in seven days with T cell subpopulations similar to those seen in the active model. This model strongly suggests an initiating role for cell–mediated immunity in TIN in the rat and may provide a parallel to human TIN.

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