International Immunology, Vol. 15, No. 6, pp. 679-690,
June 2003
© 2003 Japanese Society for Immunology
Autoimmune kidney disease and lymphadenopathy in NODlpr mice are not modified by deficiency in tumor necrosis factor receptor 1 or ß2-microglobulin
1 Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia 2 Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
Correspondence to: J. Allison; E-mail: janettea{at}unimelb.edu.au
Transmitting editor: D. Tarlinton
Fas and TNFRI, two members of the tumor necrosis factor receptor family with an intracellular death domain, each play critical roles in apoptotic death of lymphocytes and certain other cell types. We determined the overlapping functions of Fas and TNFRI by breeding non-obese diabetic (NOD) mutant mice that lacked both receptors. NODlpr mice developed extensive lymphadenopathy, splenomegaly, CD4–CD8– B220+ 
ßTCR+ T cells and autoimmune kidney disease. This pathology was not modified by concomitant deficiency in TNFRI as was reported for lpr mice on a B6 background. NODlpr mice lacking CD8+ T cells, because of a null mutation in ß2-microglobulin (ß2m), also developed a similar disease profile to NODlpr animals, but the CD4–CD8– B220+ ßTCR+ T cells now derived from a CD4+ T cell lineage. These results demonstrate that, as in the autoimmune-prone MRL stain, the NOD genetic background promotes lupus nephritis-like pathology and extensive lymphadenopathy when lpr is present. Loss of TNFRI does not exacerbate the pathology caused by deficiency in Fas and loss of ß2m does not reduce it.
Keywords: autoimmunity, lupus nephritis, lymphadenopathy, non-obese diabetic
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