title: An MRL/MpJ-lpr/lpr substrain with a limited expansion of lpr double-negative T cells and a reduced autoimmune syndrome.
abstract: The autosomal recessive mutant gene, lpr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4-CD8- double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-lpr/lpr (MRL-lpr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-lpr mice. This substrain, termed MRL-lpr.II (II for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-lpr mice. However, the expansion of a double negative lpr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-lpr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-lpr mice. However, serum levels of cryoglobulins, whose major component is IgG3, are markedly diminished in MRL-lpr.II mice with a parallel decrease in IgG3. Since MRL-lpr.II mice still carry the lpr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.
authors.affiliation: Department of Pathology, University of Geneva, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Fossati
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: R
authors.initials: R
authors.lastname: Merino
authors.forename: M
authors.initials: M
authors.lastname: Iwamoto
authors.forename: J P
authors.initials: JP
authors.lastname: Aubry
authors.forename: M
authors.initials: M
authors.lastname: Nose
authors.forename: C
authors.initials: C
authors.lastname: Spach
authors.forename: R
authors.initials: R
authors.lastname: Motta
authors.forename: S
authors.initials: S
authors.lastname: Izui
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics*; D003450:Cryoglobulins / Q000096:biosynthesis; D005260:Female; D005808:Genes, Recessive; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D066298:In Vitro Techniques; D008136:Longevity / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics* / Q000276:immunology*; D013045:Species Specificity; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D003450:Cryoglobulins