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Title: Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells
Authors: Koh, D.-R. 
Ho, A.
Rahemtulla, A.
Fung-Leung, W.-P.
Griesser, H.
Mak, T.-W.
Keywords: Autoimmunity
Systemic lupus erythematosus
Issue Date: Sep-1995
Citation: Koh, D.-R., Ho, A., Rahemtulla, A., Fung-Leung, W.-P., Griesser, H., Mak, T.-W. (1995-09). Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells. European Journal of Immunology 25 (9) : 2558-2562. ScholarBank@NUS Repository.
Abstract: MRL/lpr mice develop a systemic autoimmune disease similar to systemic lupus erythematosus in humans. The mice show progressive lymphadenopathy due to the accumulation of an unusual population of CD4-8-(DN) B220+ αβ+ T cells. We bred MRL/lpr mice with mice lacking CD4+ or CD8+ T cells by gene targeting via homologous recombination in embryonal stem cells to determine the roles of these cells in the autoimmune disease. No difference in survival or autoantibody levels was noted between CD8-l-lpr and littermate controls. Interestingly, these CD8-/- lpr mice have a reduced level of B220+ DN T cells despite: the fact that the degree of lymphadenopathy was unaltered. CD4-/- lpr mice had a diminished autoimmune disease with a reduction in autoantibody production and skin vasculitits, and increased survival compared to littermate controls. However, CD4-/- lpr mice had an enhanced splenomegaly that developed massively by 16-20 weeks of age (5 to 8 greater than lpr control mice) due to the accumulation of DNB220+ T cells. In addition, there were no differences in peripheral lymph node enlargement, although the proportion of DNB220+ T cells was about twofold higher in the CD4-l- lpr mice. These cells were phenotypically identical to the DN population in control lpr mice, indicating that the accumulating DN T cells can be dissociated from the autoimmune disease in these mice. Collectively, our results reveal that the autoimmune disease is dependent on CD4+, but not CD8+ T cells, and that many of the B220+DN T cells traverse a CD8 developmental pathway.
Source Title: European Journal of Immunology
ISSN: 00142980
Appears in Collections:Staff Publications

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