Autoimmune kidney disease and lymphadenopathy in NOD/pr mice are not modified by deficiency in tumor necrosis factor receptor 1 or beta(2)-microglobulin
- Author(s)
- Catterall, T; Stockwell, D; Marshall, V; Strasser, A; Allison, J;
- Details
- Publication Year 2003-06,Volume 15,Issue #6,Page 679-690
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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(+) alphabetaTCR(+) 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 beta(2)-Microglobulin (beta(2)m), also developed a similar disease profile to NODlpr animals, but the CD4(-)CD8(-) B220(+) alphabetaTCR(+) 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 beta(2)m does not reduce it.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- MRL-LPR MICE; CD8 T-CELLS; FAMILY MEMBER BIM; COMPLEX CLASS-I; LPR/LPR MICE; LYMPHOPROLIFERATIVE DISORDERS; SYSTEMIC AUTOIMMUNITY; INDUCED APOPTOSIS; LYMPHOID ORGANS; IPR/IPR MICE
- Publisher's Version
- https://doi.org/10.1093/intimm/dxg072
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-06-01 12:00:00