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Genetic control of the spontaneous activation of CD4+ Th cells in systemic lupus erythematosus-prone (NZB × NZW) F1 mice

Genes & Immunity volume 7, pages 647–654 (2006)Cite this article

Abstract

The F1 hybrid of autoimmune hemolytic anemia-prone NZB and nonautoimmune NZW strains of mice has been studied as a murine model of systemic lupus erythematosus. Both NZB and F1 hybrid mice show age-dependent spontaneous activation of peripheral CD4+ T cells as reflected by the elevated frequencies of CD4+ T cells positive for CD69 early activation marker. Both strains also show age-dependent abnormal decrease of the frequencies of CD62L+ naive CD4+ T cells and/or NTA260+ memory CD4+ T cells in the spleen. We studied the multigenic control of these abnormal features of peripheral CD4+ T cells in (NZB × NZW) F1 × NZW backcross mice by quantitative trait loci mapping and by association rule analysis. The abnormally elevated frequencies of CD69+CD4+ T cells and decreased frequencies of CD62L+ naive and/or NTA260+ memory CD4+ T cells were under the common genetic control, in which the interaction between MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell activation) on chromosome 12, plays a major role. The allelic effects of these loci likely predispose CD4+ T cells to the loss of self-tolerance, and are responsible for the accelerated autoimmune phenotypes of (NZB × NZW) F1 hybrid mice.

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Acknowledgements

This work is supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan. We thank Noriko Isoyama and Atsuko Kusano for the management of the mouse colonies and Noriko Iida for technical assistance.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Toin Human Science and Technology Center, Toin University of Yokohama, Yokohama, Japan

    T Fujii, Y Iida, M Yomogida, K Ikeda, T Haga, Y Jikumaru, M Ninami, N Nishimura, Y Kodera, Y Inada & H Nishimura

  2. Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan

    T Shirai & S Hirose

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  1. T Fujii
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Fujii, T., Iida, Y., Yomogida, M. et al. Genetic control of the spontaneous activation of CD4+ Th cells in systemic lupus erythematosus-prone (NZB × NZW) F1 mice. Genes Immun 7, 647–654 (2006). https://doi.org/10.1038/sj.gene.6364342

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