International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)


G17. Multigenic Control of the Spontaneous T cell Activation in Systemic Lupus Erythematosus(SLE)-Prone (NZB x NZW)F1 Mice

Masato Yomogida1, Hisashi Hasegawa1, Noriko Takahashi1, Junichi Toei1, Kimiko Ochiai1, Yo Kodera1, Ayako Matsushima1, Misao Hiroto1, Yuji Inada1, Sho Ishikawa2, Sachiko Hirose2, Toshikazu Shirai2 and Hiroyuki Nishimura1
1Toin Human Science and Technology Center, Department of Biomedical Engineering, Toin University of Yokohama, Yokohama 225-8502, Japan.
2Department of Pathology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.

Systemic lupus erythematosus(SLE) is an autoimmune disease characterized by the production of autoantibodies directed to double-stranded DNA, and by the development of immune-complex-type glomerulonephritis. F1 hybrid between the autoimmune-prone New Zealand Black(NZB) and phenotypically normal New Zealand White(NZW) strains develops an autoimmune disease closely resembling to human SLE. In these mice, B1 cells(CD5+ B cells) are known to be responsible for the production of autoantibodies. However, development of autoimmune phenotypes typical of SLE has been shown to be dependent on the presence of auto-reactive CD4+ Th cells that enhance autoantibody production. At least two NZB alleles have been shown to be involved in the abnormal B1 cell functions in these mice. However, genetic predisposition to the production of pathogenic CD4+ T cells has remained unknown. In these mice, there is an age-associated increase of the frequencies of peripheral CD4+ T cells expressing CD69, an early activation marker of T cells. To study the genetic control of the spontaneous activation of CD4+ T cells in these mice, we analyzed the progeny of (NZB x NZW)F1 x NZW backcross mice (n = 300) for the quantitative trait loci regulating the frequencies of splenic CD69+CD4+ T cells. We observed a suggestive linkage to Cinda2 locus on the centromeric region of chromosome 12 that has been reported to be responsible for the regulation of the cytokine-induced activation of T cells. Nevertheless, spontaneous activation of CD4+ T cells appears to be under multigenic control which is distinct from that responsible for the abnormal B1 cell functions in these mice.


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