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

Par Conseil national de recherches du Canada

DOI	Trouver le DOI : https://doi.org/10.4049/jimmunol.169.7.4025
Auteur	Rechercher : Sobel, Eric S.; Rechercher : Morel, Laurence; Rechercher : Baert, Raquel; Rechercher : Mohan, Chandra; Rechercher : Schiffenbauer, Joel; Rechercher : Wakeland, Edward K.
Format	Texte, Article
Résumé	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.
Date de publication	2002-10-01
Maison d’édition	American Association of Immunologists
Dans	The Journal of Immunology 169, nº 7 (1 octobre 2002) : 4025–4032.
Langue	anglais
Publication du CNRC	Cette publication n’est pas du CNRC Ce sont des publications qui ont été rédigées par un auteur du CNRC, mais avant que celui-ci soit employé du CNRC.
Numéro du CNRC	1993
Numéro NPARC	9148421
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Identificateur de l’enregistrement	71cf9c20-92a5-47d7-bd08-edf311d0d36c
Enregistrement créé	2009-06-25
Enregistrement modifié	2022-10-17

Date de modification :: 2025-11-14