Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis.
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.
Sireci
Guido
G
Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy. sireci@unipa.it
Russo
Domenica
D
Dieli
Francesco
F
Porcelli
Steven A
SA
Taniguchi
Masaru
M
La Manna
Marco Pio
MP
Di Liberto
Diana
D
Scarpa
Francesco
F
Salerno
Alfredo
A
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
D001323:Autoantibodies; D011948:Receptors, Antigen, T-Cell