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Genetic dissection of systemic Lupus Erythematosus pathogenesis: evidence for functional expression of Sle3/5 by non-T cells

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.4049/jimmunol.169.7.4025
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FormatText, Article
Abstract
On the non-autoimmune C57BL/6 (B6) background, the chromosome 7-derived lupus susceptibility loci Sle3 and Sle5 have been shown to mediate an elevated CD4:CD8 ratio with an increase in activated CD4+ T cells, decreased susceptibility to apoptosis, and a break in humoral tolerance. Development of subcongenic strains has subsequently shown that the elevated CD4:CD8 ratio is due to Sle3 but that both loci contribute to the development of autoantibodies. To elucidate the functional expression patterns of these loci, adoptive transfer experiments were conducted. All possible combinations of bone marrow reconstitution, including syngenic, were conducted between the congenic B6 and B6.Sle3/5 strains. It was found that the Sle3/5 locus was functionally expressed by bone marrow-derived cells, but not by host cells, and that the elevated CD4:CD8 phenotype could be reconstituted in radiation chimeras. Using Ly5-marked congenic strains and B6 host mice, additional experiments surprisingly demonstrated that the elevated CD4:CD8 ratio was neither an intrinsic property of the T cells nor of single positive thymocytes. Allotype-marked chimeras indicated that autoantibody production by B cells was also an extrinsic property, as shown by the fact that B cells without the Sle3/5 interval contributed to autoantibody production. These experiments strongly suggest that a gene within the B6.Sle3/5 interval was expressed by a bone marrow-derived, nonlymphocyte population in the thymus and periphery and was affecting T cell selection and/or survival.
Publication date
PublisherAmerican Association of Immunologists
In
  • The Journal of Immunology 169, no. 7 (1 October 2002): 4025–4032.
LanguageEnglish
NRC publication
This is a non-NRC publication

"Non-NRC publications" are publications authored by NRC employees prior to their employment by NRC.

NRC number1993
NPARC number9148421
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Record identifier71cf9c20-92a5-47d7-bd08-edf311d0d36c
Record created2009-06-25
Record modified2022-10-17
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