Immunoregulatory role ofJα281 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 Vα14Jα281 chains paired with some Vβ domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jα281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jα281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jα281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG₃ subclass. In spleens of aged Jα281 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 Jα281⁺ cells, probably associated with the activation of marginal zone B cells.