title: Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy. sireci@unipa.it
authors.forename: Guido
authors.initials: G
authors.lastname: Sireci
authors.forename: Domenica
authors.initials: D
authors.lastname: Russo
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Marco Pio
authors.initials: MP
authors.lastname: La Manna
authors.forename: Diana
authors.initials: D
authors.lastname: Di Liberto
authors.forename: Francesco
authors.initials: F
authors.lastname: Scarpa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Salerno
mesh_terms: D000375:Aging; D000818:Animals; D001323:Autoantibodies; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D011948:Receptors, Antigen, T-Cell